Newer AD research news



Subject: NIA News Release: New Studies Suggest Ways to Clear AD Plaques


>
> **New Studies in Mice Suggest Ways to Clear Damaging
> Alzheimer's Amyloid Plaques**
>
> (This news release can be found on our web site at
> http://www.alzheimers.org/nianews/nianews53.htm)
>
> Two new research findings suggest that boosting normal, protective
> processes in the brain might help degrade or prevent damaging protein
> plaques associated with Alzheimer's disease (AD). In one publication,
> researchers at The Salk Institute and colleagues at other institutions
> found that gene transfer of the enzyme neprilysin may help clear a
> protein that forms amyloid plaques in humans. The experiments -- in mice
> -- are an important step in the development of an alternative approach
> to controlling AD and suggest closer study of the potential for
> neprilysin therapy.
>
> The findings, by Fred H. Gage, Robert A. Marr, and Inder M. Verma at The
> Salk Institute for Biological Studies, Eliezer Masliah at the University
> of California San Diego and Atish Mukherjee and Louis B. Hersh at the
> University of Kentucky, Lexington, are reported in the latest issue of
> The Journal of Neuroscience.*
>
> The Gage report comes on the heels of another study, reported March 3,
> 2003, in the online version of Nature Medicine, by Jens Husemann,
> Columbia University, New York, Tony Wyss-Coray, Veterans Affairs Palo
> Alto Health Care System and Stanford University in California, and
> colleagues. Husemann's group found that certain cells in the brain,
> called astrocytes, can degrade the beta amyloid peptide in cell
> cultures. While not yet tested in an animal model, the study's finding
> that astrocytes can be effectively mobilized at the cellular level
> suggests yet another possible target for potential therapies for AD.
>
> "In recent years, we have been looking at ways to battle amyloid," says
> Brad Wise, Program Director, Fundamental Neuroscience, the National
> Institute on Aging's (NIA) Neuroscience and Neuropsychology of Aging
> Program. "Most studies have focused on blocking the production of
> proteins that form AD plaques. Both of these studies suggest how we
> might clear amyloid even if it does build up in the brain. These are
> very new ways of addressing the problem."
>
> The Gage research was funded by the NIA, part of the National Institutes
> of Health, U.S. Department of Health and Human Services. Funding was
> also provided by the Alzheimer's Association, the Canadian Institutes of
> Health Research, and other funds and foundations. The Husemann study was
> funded by the NIA and the Alzheimer's Association.
>
> Scientists have known for many years that amyloid plaques in the brain
> are a hallmark feature of AD in humans. Studies on the etiology of the
> disease have shown that the plaques are formed when the larger amyloid
> precursor protein (APP) is broken up, resulting in the formation of beta
> amyloid protein fragments, or abeta peptides, that clump together to
> form insoluble amyloid plaques in certain areas of the brain with AD. It
> has been hypothesized that one approach to preventing AD or delaying its
> clinical symptoms might be to interfere with the production of beta
> amyloid or, more recently, to degrade beta amyloid or its plaques.
>
> Previous research has shown that neprilysin is reduced in areas
> vulnerable to plaque formation and that mice without the neprilysin gene
> have increased levels of beta amyloid in the brain. Test tube studies
> have also shown that neprilysin could help stop the production of beta
> amyloid.
>
> The current experiments reported by Gage and colleagues represent the
> first demonstration that increased levels of neprilysin decrease the
> deposition of amyloid in an animal model. In this study, the team
> injected gene vectors carrying human neprilysin into the
> amyloid-containing brains of transgenic mice. The gene transfer was
> concentrated in two areas of the brain, the hippocampus and the frontal
> cortex, both areas where plaque formation occurs in humans.
>
> At the end of the treatment, the researchers reported, introduction of
> the neprilysin appeared to increase degradation or reduce the growth of
> already existing plaques. Plaques found in areas strongly "expressing"
> neprilysin, near the injection sites, were found to be smaller and more
> compact than in other regions of the brains. In some cases, what the
> researchers call plaque "load" was reduced to less than half that found
> in comparable, untreated areas. There was also evidence that
> neurodegeneration, neuronal cell damage, was reduced after the
> neprilysin gene transfer.
>
> "If we find a way to shift the balance between amyloid production,
> clearance, and degradation, I believe we can find a way to interfere
> with the processes involved in Alzheimer's disease," says Gage. "Further
> study will help define the role of neprilysin in regulating amyloid and
> possibly treating or preventing AD."
>
> Astrocytes, a type of cell which supports, nourishes, and protects
> neurons in the brain, are found around and are in contact with AD
> plaques. Husemann and colleages theorized that astrocytes near the AD
> plaques may not only immobilize or bind to abeta peptides in the brain,
> but might also degrade the abeta, which they found to be the case with
> adult mouse astrocytes.
>
> The team then set out to see if adult astrocytes could also "process"
> abeta deposits from brain tissue. They incubated adult astrocytes on
> brain sections of transgenic mice making human APP. After 24 hours
> incubation with astrocytes, the area of the hippocampus occupied by
> abeta was reduced by 40 percent, Husemann and colleagues found. "The
> findings raise the intriguing possibility that defects in astrocyte cell
> clearance of abeta may contribute to the formation of AD plaques," notes
> Husemann. "Harnessing the protective function of these cells may be a
> strategy for AD prevention and treatment."
>
> The NIA leads the Federal effort to support and conduct basic, clinical,
> and social and behavioral studies on aging and on AD. It supports the
> Alzheimer's Disease Education and Referral (ADEAR) Center, which
> provides information on AD research.
>
> ADEAR's website can be viewed at http://www.alzheimers.org, where
> several publications may be found on the causes and course of AD,
> including the new publication "Alzheimer's Disease: Unraveling the
> Mystery" at http://www.alzheimers.org/unraveling/index.htm and the
> detailed "Progress Report 2000" at http://www.alzheimers.org/prog00.htm
> which describes the broad Federal research program on AD.
>
> The public and health professionals may also call ADEAR toll free,
> 1-800-438-4380. Press releases, fact sheets, and other materials about
> aging and aging research can be viewed at the NIA's general information
> website, http://www.nia.nih.gov.
>
> *The Journal of Neuroscience findings were publicly released March 25,
> 2003, at 5 p.m. Eastern Time, appearing in the journal issue dated March
> 15, 2003.

Use today wisely,
It's the only one we get.

Oh, for so short a time,
we are on loan to each other.

Jim

Can Painkillers Prevent Alzheimer's?: Lab study shows some can dissolve damaged cells
By Ed Edelson
HealthScoutNews Reporter

WEDNESDAY, March 12 (HealthScoutNews) -- A study of diseased brain cells has produced evidence that could support the theory that common over-the-counter painkillers can help prevent or even treat Alzheimer's disease, researchers report.

The discovery, while preliminary, could open the way to early detection and prevention of the brain-robbing condition, says Dr. Jorge R. Barrio, a professor of molecular and medical pharmacology at the University of California at Los Angeles (UCLA) and leader of the group reporting the finding in the March 31 issue of the journal Neuroscience.

Tests done at UCLA show painkillers such as ibuprofen and naproxen bind to the amyloid plaques that are believed to be responsible for progressive destruction of brain cells in Alzheimer's disease, Barrio says. That binding could help dissolve those plaques and prevent formation of new ones, he adds.

The key to the finding was the discovery that a chemical whose long name is abbreviated FDDNP will bind to the damaged brain cells seen in Alzheimer's disease and produce a distinctive glow. The UCLA researchers took samples of damaged brain fibers, added FDDNP and the painkillers, and saw that glow.

Not every painkiller binds to the plaques, Barrio says. Most notably, aspirin does not. But further studies with ibuprofen and naproxen indicated those drugs could inhibit plaque formation.

Barrio's goal is prevention of Alzheimer's disease when it is detected in its earliest stages. He acknowledges that reaching that goal will take some time. "The next step is to do the test with patients," he says. "Perhaps we can make the same kind of progress against dementia that we have made against heart disease and cancer."

The UCLA researchers have reported that a positron emission scan can show early brain damage in Alzheimer's patients when FDDNP is injected into them. Early detection now is useless, he says, since there is no treatment for Alzheimer's disease. If the anti-inflammatory drugs fulfill their promise, "early diagnosis could have a meaning," he says.

Bill Thies, vice president for medical and scientific affairs at the Alzheimer's Association, takes a more cautious approach. "This adds support to the idea that some anti-inflammatory drugs might work and some might not," he says. He is also cautious about the epidemiological studies that found a relationship between intake of anti-inflammatories and a reduced incidence of Alzheimer's disease.

"Those studies showed correlation but not causation," Thies says.

And it is very early in the search for a treatment, he says: "It is important to recognize that this is a test case sort of study. It is an interesting way to find the best new drug to treat people with. But ultimately you must show that these compounds change the progression of the disease."

Copyright © 2003 ScoutNews, LLC. All rights reserved.
Last updated 3/12/2003

Cholinesterase Inhibitors Show Broader Benefits
by Hakon Heimer
Alzheimer Research Forum

10 January 2002. A meta-analysis of clinical trials indicates that cholinesterase inhibitors do more than boost cognitive test scores in Alzheimer's patients. As reported in yesterday’s Journal of the American Medical Association, the drugs as a group also improve psychiatric symptoms and enhance daily function.

Cholinesterase inhibitors (ChEIs) clearly have a beneficial effect in mild to moderate Alzheimer's (though whether they do this by inhibiting ChE has recently been questioned; see ARF related news item). There is also evidence that this benefit extends beyond cognitive decline to include effects on symptoms such as hallucinations, paranoia, agitation, and affective disturbances. There also is evidence that ChEIs might improve functional measures—either the early declines in instrumental activities of daily living (IADL), such as use of the telephone or ability to maintain drug regimens, or the later declines in basic activities of daily living (ADL), such as eating or dressing. However, because ChEI clinical trials that evaluated these measures have had conflicting results, Kristine Yaffe of the University of California, San Francisco, Nhi-Ha Trinh of Massachusetts General Hospital in Boston, and colleagues decided to examine some of these trials in a meta-analysis.

The authors included 29 studies of many different ChEIs that met various criteria, including being parallel-group or crossover randomized, double-blind, placebo-controlled trials of outpatients with mild to moderate AD. Among these trials, 16 had neuropsychiatric and 18 had functional measures.

Of the 16 studies measuring neuropsychiatric manifestations, the six trials using the Neuropsychiatric Inventory (NPI) showed a small but statistically significant benefit from ChEIs, whereas the 10 trials using the Alzheimer Disease Assessment Scale, noncognitive (ADAS-noncog) showed a nonsignificant trend toward a benefit. (In the case of three trials that used both instruments, the researchers included only the NPI in their analyses, because the ADAS-noncog does not include measures of aggressiveness and anxiety, and may be less sensitive to change.)

Of the 18 studies measuring daily function, the 14 that measured ADL showed a nonsignificant trend toward benefit from ChEIs, whereas the 13 trials that measured IADL showed a small but statistically significant benefit. "However," the authors note, "because functional impairment is closely linked to cognitive impairment, it is unknown whether the benefit to functional impairment from [ChEIs] is due to reducing cognitive impairment or an independent mechanism."

The authors found that each of the ChEI's had similar beneficial effects, though they acknowledge that their analysis had limited statistical power to make this assessment. "We believe our results are the first attempt to quantitatively synthesize the efficacy of a variety of [ChEIs] for neuropsychiatric symptoms and functional impairment, and to suggest a modest benefit [in these outcomes]," the authors write.

Reference:
Trinh H, Hoblyn J, Mohanty S, Yaffe K. Efficacy of cholinesterase inhibitors in the treatment of neuropsychiatric symptoms and functional impairment in Alzheimer disease. JAMA. 2003 Jan 8;289(2):210-6.

Studies Say Vegetables Good Against Alzheimer's
Mon Feb 17, 4:06 PM ET
(c) Reuters

CHICAGO (Reuters) - A diet high in unsaturated, unhydrogenated fats such as vegetable products and some oils may help lower the risk of Alzheimer's Disease but antioxidant vitamins have no such protective effect, according to two separate studies published on Monday.

Doctors at Rush-Presbyterian-St. Luke's Medical Center in Chicago said they reached their conclusions on the fat question after examining 815 people aged 65 and older who did not have Alzheimer's at the start of a nearly four-year study.

Those in the study were asked to recall their dietary habits during a more than two-year period before the study began.

At the end of the study the researchers found that 131 people had developed Alzheimer's, the debilitating disease that leads to memory loss and eventual physical incapacity.

People who consumed the most saturated fat -- the kind of fat that comes from meat, poultry, dairy products and palm or coconut oils -- had 2.3 times the risk of developing Alzheimer's compared with those who consumed the lowest amount of saturated fats, the researchers said.

REASONS UNCLEAR

The study did not speculate on why the different kinds of fats were associated with different risks for the disease. It said that previous research suggests diets high in total fat, saturated fat and dietary cholesterol may increase the risk of dementia for reasons that are not clear.

The study, published in the February issue of the Archives of Neurology, was financed by the National Institute on Aging, part of the U.S. National Institutes of Health.

In a second study published in the same journal, researchers at Columbia University in New York concluded that carotenes and vitamins C and E obtained from diet or through supplements are not associated with a decreased risk of Alzheimer's.

The question arises because antioxidants -- vitamins and other nutrients found in food -- appear to reduce cellular damage caused by free radicals. Free radicals are tiny particles from normal metabolism that may damage neurons, possibly leading to Alzheimer's.

The report said a look at 980 people who were free of dementia at the beginning of a four-year study found that 242 developed Alzheimer's over the course of the research, and that consumption of carotenes or vitamins A and E had no protective effect.

The same journal carried a third study from researchers at the University of California School of Medicine in San Diego that said post-menopausal women with Alzheimer's given estrogen therapy had no improvement in their cognitive function after one year of treatment.

Some previous studies had suggested estrogen helped in such cases. The drug given the women was Wyeth's "Premarin."

High-Fat Diets Not Linked to Dementia: Study finds no connection between Alzheimer's and cholesterol levels
By Jennifer Thomas
HealthScoutNews Reporter
ScoutNews LLC

MONDAY, Dec. 23 (HealthScoutNews) -- Dementia is a terrifying disease, one that millions of seniors would want nothing more than to have some means of preventing.

However, eating a low-fat diet and keeping your cholesterol down doesn't seem to help matters, a new Dutch study says.

Researchers followed 5,395 men and women with a mean age of 68 for six years, analyzing their intake of dietary fat and their blood cholesterol levels. Over the course of the study, 197 people developed dementia.

The study found no link between high-fat diets or elevated cholesterol and the development of dementia.

However, researchers caution that more research needs to be done to confirm the findings.

"We think it is premature to conclude from our observational study that cholesterol or cholesterol-affecting fats are not associated with risk of dementia," write the authors from the Erasmus Medical Center in Rotterdam, The Netherlands. "Larger, prospective studies with longer follow-up periods are needed to confirm our findings."

The study appears in tomorrow's issue of Neurology.

Researchers studied two types of dementia: Alzheimer's disease and vascular dementia. In the study, 146 developed Alzheimer's disease and 29 developed vascular dementia, which is usually caused by multiple small strokes in the brain.

The precise cause of Alzheimer's is unknown. However, a hallmark of the progressive disease is the excessive formation of amyloid plaques, clumps of protein fragments that accumulate around the neurons in the brain.

About 4 million Americans have Alzheimer's disease, making it the most common form of dementia in the elderly, according to the Alzheimer's Association.

Previous research has shown that cholesterol-lowering drugs called statins lower the risk of developing dementia, says Dr. Irene Litvan, director of the movement disorders program at the University of Louisville School of Medicine.

Research has also indicated that dietary fat and high cholesterol could contribute to the formation of amyloid proteins.

In their analysis of dietary intake of fat, researchers looked at several types of fat, including trans fats -- which are thought to be particularly bad for the cardiovascular system -- and polyunsaturated fatty acids, which research has shown has anti-inflammatory properties and may protect against some diseases. Polyunsaturated fats are those found in olive oil and fatty fish such as salmon.

No kind of fat had any effect on the development of dementia, according to the study.

Litvan says it's far too soon to heap on the mashed potatoes and gravy with abandon.

"It's a good study, but it's a small study," she says. "The number of people who actually develop the disease is not huge. You never have a definitive answer unless you have a large number of patients participating or a large number who develop the disease."

And high cholesterol and a fatty diet have been shown to contribute to another major killer: cardiovascular disease.

"I maybe wouldn't watch my intake of fats to prevent dementia, but I would watch it for this reason," Litvan says.

Alzheimer's Caregivers at Greater Risk of Blood Clotting: Serious life stress for these people may predict risk of heart problems
HealthScout LLC

TUESDAY, Feb. 4 (HealthScoutNews) -- People looking after loved ones with Alzheimer's disease could be at increased risk of excessive blood clotting.

That's the finding of a new study in the January-February issue of the journal Psychosomatic Medicine.

The University of California, San Diego-led study included 54 men and women providing home care for a spouse with Alzheimer's disease. The researchers collected information from each person about stressful life circumstances, unrelated to their caregiver role, in the four weeks before the start of the study.

Each person in the study was evaluated for depression, and information was collected about their overall health and medication use. The researchers took a blood sample from each person to measure levels of three indicators of excessive blood clotting.

The study found the caregivers who reported a higher number of recent negative life events (for example, the death of a child from cancer) were more likely to have higher levels of an excessive blood clotting indicator called fibrin D-dimer (DD).

The researchers note that an increase in DD, even within the normal range, may predict heart attacks and other coronary problems in healthy people, as well as in people with coronary disease.

The study indicates that serious life stress may cause excessive blood clotting in these caregivers. This hypersensitivity to blood clotting can play a major role in clogging and blockage of coronary arteries, which are the major vessels that carry blood to the heart.

Holding Onto Memory: Some early-stage Alzheimer's patients can compensate and do well on memory tests
HealthScout LLC

WEDNESDAY, Feb. 5 (HealthScoutNews) -- People with early-stage Alzheimer's disease can engage additional brain areas to do well on memory tests.

A Canadian study, which appears in the current issue of the Journal of Neuroscience, is the first to find a link between this compensatory activity in the prefrontal regions of the brains of people with early-stage Alzheimer's and their ability to perform well on memory tests.

This compensatory effect doesn't last forever and diminishes as the mind-robbing disease progresses. Even so, the study authors feel it's an area that warrants further investigation. It may lead to treatments that can extend the compensatory effect and delay the degenerative effects of Alzheimer's.

The study included 12 healthy older adults and 11 older adults with probable early-stage Alzheimer's disease. All of the people with Alzheimer's were taking medication for their cognitive impairments.

All the study subjects performed memory tasks that were flashed on a computer screen. Overall, the people with Alzheimer's performed less accurately than the healthy study subjects.

However, some of the people with Alzheimer's did score within the normal range on the memory tests. The researchers found these people had more expansive activity in their brain's prefrontal network than the people with Alzheimer's who made more errors in the memory tests.

New Studies a Mixed Bag for Diet and Alzheimer's: One says vitamins won't help, the other says vegetable fats might
By Jennifer Thomas
HealthScoutNews Reporter
HealthScout LLC

TUESDAY, Feb. 18 (HealthScoutNews) -- Two new studies offer mixed news when it comes to staving off Alzheimer's disease through your diet.

One says vitamins C and E and carotenes don't decrease the risk of getting Alzheimer's. However, the second says that eating a diet that's low in saturated and hydrogenated fats and high in unsaturated fats just might help fend off the disease that afflicts 4 million Americans.

Both studies, which were funded by the National Institute on Aging, appear in the February issue of the Archives of Neurology.

"One of the things we're hoping for at the National Institute on Aging," says Marcelle Morrison-Bogorad, associate director of the institute's Neuroscience and Neuropsychology of Aging Program, "is that eventually in our attempts to slow the development of Alzheimer's we will have a combination of lifestyle changes plus very directed, specific drugs that together will give us a chance of really fighting this dreadful disease."

In the study on vitamins, researchers followed 980 elderly patients, who did not have dementia at the outset of the study, for four years. The participants answered questionnaires about their eating habits at the beginning of the study and several times during the next four years.

During the course of the study, 242 people developed Alzheimer's disease. Researchers found no link between their intake of antioxidant vitamins and whether they got the disease.

About one in 10 people over 65 and nearly half of those over 85 have Alzheimer's disease, according to the Alzheimer's Association. While the exact cause of the disease is unknown, researchers believe that free radicals, tiny particles generated by normal metabolism, can over time damage neurons in the brain and contribute to dementia.

Antioxidants reduce the damage done by free radicals, so researchers had hoped that eating foods or taking supplements high in antioxidants would help prevent the disease.

Though that hope wasn't borne out in this study, don't stop taking your vitamins E and C just yet, Morrison-Bogorad says.

Other studies have shown antioxidants can help stave off dementia. The National Institute on Aging is currently funding randomized, double-blind, placebo-controlled clinical trials -- the gold standard of scientific testing -- on antioxidants and Alzheimer's.

The people in that study are taking 10 times the dosage of vitamin E that people reported they took in this study, Morrison-Bogorad says. "That may change the outcome," she says.

In the study on fats and Alzheimer's, researchers looked at random sample of 815 Chicago-area people ages 65 and older who did not have Alzheimer's disease.

Study participants had completed questionnaires about their eating habits more than two years before the study started.

After four years, researchers identified 131 people with dementia.

They found those who ate diets that were low in saturated fats and hydrogenated fats and high in unsaturated fats had a decreased risk of developing Alzheimer's.

Unsaturated fats are found in vegetables oils (such as canola, corn, safflower or olive), in nuts and seeds, in liquid margarine and mayonnaise.

Saturated fats are those found in animal products, such as butter, red meat, whole milk and cheese.

Snacks foods, such as commercially-produced baked goods, pretzels and other chips, and hard margarine are sources of hydrogenated fats. Hydrogenation is a chemical alteration of vegetable oils that occurs during the manufacturing process.

"What's important is that so many people are under the impression that they should cut fat out of their diets, when in fact the vegetables fats are very good for you and you should think about getting a little at every meal," says Martha Clare Morris, lead author of the study and an epidemiologist at Rush-Presbyterian-St. Luke's Medical Center in Chicago.

Study participants were divided into five groups based on their intake of the various kinds of fats. Those in the group that consumed the least of the "bad" fats and the most of the "good" fats had an 80 percent less chance of developing Alzheimer's than those in the group that consumed the most "bad" fats and the least "good" fats.

The group with the least incidence of Alzheimer's ate about 38 grams of "good" fats per day, Morris says, while those with the highest incidence of Alzheimer's ate only about 19 grams of "good" fats per day.

Morrison-Bogorad says the study is very interesting, but needs to be confirmed by other research.

Read the complete article here...

CES

I'm so happy to see you posting again. I have missed you. How are things in your corner of the world?

Vicki

Sugarlips

Paper from The Special Parkinson's Research Interest Group (SPRING) within the Parkinson's Disease Soc of the UK.

Note that Ubiquitin mentioned in the article should not to be confused with Ubiquinone which is another name for Co-enzyme Q10.


A common theme in Neurodegenerative Diseases?

Professor Mayer gave a presentation at the Derby Forum entitled “Dementia with Lewy Bodies”. What follows encapsulates the core of what he said and is abstracted from a recent paper on:

Defects in the ubiquitin proteasome pathway of intracellular proteolysis
“UPP” is the abbreviation to remember. It stands for the “Ubiquitin-Proteasome Pathway”. The key to new drug-based therapies for Parkinson’s Disease could be found by understanding this intracellular mechanism better.

The UPP1 is the mechanism which is, in all animal cells, responsible for clearing up the protein garbage that results from normal metabolism. There is increasing evidence that when this mechanism becomes defective or is overwhelmed, degenerative disease occurs. What is more, it seems that this is a common factor in a whole range of diseases including not only the neurodegenerative diseases such as PD, Alzheimer’s (AD) and Dementia with Lewy Bodies but also others such as liver necrosis. A common characteristic of such diseases is the presence of protein aggregates in cells – Lewy bodies in PD, neurofibrillary tangles in AD and Mallory bodies in alcoholic liver disease – which give a clue to what is going on.

So how does the UPP work and why is it so important?

The first step is the activation of molecules of Ubiquitin by a pair of enzymes known simply as E1 and E2. The next step is the movement of the activated Ubiquitin molecules throughout the cell until they find damaged or mis-folded proteins which, if not removed, would poison the cell. Another pair of enzymes, E3 and E4, chemically stick them to the target protein molecule as a chain of Ubiquitin molecules at least 4 units long. This effectively labels the protein for disposal by a Proteasome.

When a “Ubiquitylated” protein comes near a Proteasome (which is an Organelle, i.e. a specialized structure that carries out a distinct cellular function), the Proteasome recognises the protein as one to be disposed of and ingests it and breaks it up into its constituent peptides or amino acids which can then be recycled. In the process the Ubiquitin molecules are released to participate in another cycle.

It follows that, if harmful proteins are not removed because of the malfunctioning of any part of the UPP, they will build up and eventually kill the cell. At this point, however, another process can intervene and direct the harmful protein to accumulate and be deposited in tangles or Lewy bodies. Thus the formation of Lewy bodies, Alzheimer tangles and Mallory bodies in the liver are examples of a defence mechanism which occurs when the usual way of disposing of the protein garbage fails. Ubiquitin is found bound to the protein in these inclusions which gives evidence that the cause of their formation is related to a breakdown of the UPP. Proteins from the proteasome and enzymes of the UPP are also found in the inclusions.

The above, however, is a one-sided oversimplification. There is now much evidence that the UPP is central not only to the disposal of damaged and mis-folded proteins, but also to the disposal of ALL proteins which need to be removed whether they have been produced in error, or in excess or have merely completed the legitimate work they were produced for in the first place. In other words the UPP is one of the essential regulatory mechanisms in all cells of the body.

The chemistry of all living things is totally protein-centric. Not only do proteins form the structures of the body - the flesh, bones, nerves and blood - but also predominantly the ‘tools’ that the body uses to maintain itself – the DNA, RNA, the enzymes and biochemical agents and messengers. The genes produce proteins which have particular functions and, once these functions in a certain context have been fulfilled, those proteins have to be removed. This is the role of the UPP. Of course this is unimaginably complex and subtle. There are thousands of types of protein in each cell and the chemical balance can be catastrophically upset if some proteins are removed when they should not be and others are left behind when they should be removed. Degenerative diseases happen when there is a failure to get this balance quite right.

The four enzymes mentioned above, E1, E2, E3 and E4 are actually four groups of enzyme. Subtly different forms of each are involved in different circumstances so that different proteins are labelled for disposal in different contexts. Indeed it is likely to be the case that sometimes the UPP is too effective because it removes a type of protein which itself is regulating a second protein which in the wrong concentration causes a disease condition. So sometimes the effectiveness of the UPP enzymes or Proteasomes may need boosting and at other times inhibiting. Here there is a connection with cancer research because in PD the deficiency in the UPP causes cell-death whereas in cancer cells the signals being given to self-destruct are not getting through or obeyed.

Rest here.

ces

Coalition for the Advancement of Medical Research Supports President’s Call to Ban Reproductive Cloning But Opposes Ban on Therapeutic Cloning

Washington, DC—January 28, 2003—In the President’s State of the Union speech this evening, he called for a ban on all forms of human cloning, which would include both reproductive (which seeks to create babies), and therapeutic cloning, also called somatic cell nuclear transfer, (which seeks to produce stem cells to cure disease). The Coalition for the Advancement of Medical Research (CAMR)—comprised of the nation’s leading patient groups, universities, and scientific societies—supports the President’s call to ban reproductive cloning but opposes any efforts to ban therapeutic cloning.
“CAMR has repeatedly called on Congress to act quickly to pass a ban on human reproductive cloning and the majority of Americans also support this view. However, a ban on therapeutic cloning would not only dash the hopes of millions of Americans suffering from Parkinson’s, diabetes, ALS, spinal cord injuries, cancer, and other insidious diseases, it does not represent the opinion of the majority of the American people, the National Academy of Sciences, and the nation’s leading scientists and Nobel laureates” said Michael Manganiello, President of CAMR.

“As a police officer, I worked to uphold the law and ensure that the rights of my fellow citizens were protected. I never thought I would someday have to fight for my own right to a cure,” said Kris Gulden, who will testify tomorrow before the Subcommittee on Science, Technology and Space, U.S. Senate Commerce, Science, and Transportation Committee. Ms. Gulden was spinal cord injured in 1998 from a biking accident and is paralyzed from the chest down. “Allowing research using therapeutic cloning to move forward is critically important to me and others like me. It’s our right to have access to potentially life-saving treatments and I hope the U.S. Congress will enact laws to protect these rights and protect our hope,” she added.

Somatic cell nuclear transfer is about saving and improving lives. It is fundamentally different from human reproductive cloning; it produces stem cells, not babies. In somatic cell nuclear transfer, the nucleus of a donor’s unfertilized egg is removed and replaced with the nucleus of a patient’s own cells, like a skin, heart, or nerve cell. These types of cells are called somatic cells. The goal is to develop stem cells that will not be rejected or destroyed by the patient’s immune system. No sperm is used in this procedure. The cells are not transplanted into a womb. The unfertilized egg cells are stored in a petri dish to become a source of stem cells that can be used to treat life-threatening medical conditions. Somatic cell nuclear transfer aims to treat or cure patients by creating tailor-made, genetically identical cells that their bodies won’t reject. In other words, somatic cell nuclear transfer could allow patients with diseases and conditions like cancer, diabetes, ALS, Parkinson’s, spinal cord injuries and many more to be cured using their own DNA.

Article

Coalition for the Advancement of Medical Research

ces

Roche Diagnostics Is Validating New Marker Candidates for Diagnosis of Alzheimer Disease

HANOVER, GERMANY--(INTERNET WIRE)--Jan 22, 2003 -- Since entering into a cooperation project with Roche Diagnostics GmbH of Mannheim in 1999, Hanover-based biotechnology firm BioVisioN has identified a number of proteins that may enable early diagnosis of Alzheimer's Disease and distinguish it from other forms of dementia. The cooperation between BioVisioN and Roche Diagnostics GmbH is therefore now entering a new phase.

BioVisioN began investigating the volumes of small proteins (peptides) in cerebrospinal fluid in 1999. Working together with Roche Diagnostics, this procedure was used successfully in 2000 and 2001 on samples taken from Alzheimer's sufferers, patients with other forms of dementia and control patients. This enabled molecules to be identified that changed content specifically in the cerebrospinal fluid of Alzheimer's patients. Several patents have been filed on the basis of these findings, and another is currently being registered. Having assessed the data, Roche Diagnostics has now decided to test large groups of patients for the presence of the most promising of these peptides in serum, and it is currently developing an appropriate testing system.

More than a million people are afflicted with dementia in Germany alone, more than half of them in the form of Alzheimer's Disease. This is typically found in elderly people and -- due to its clinical phenotype -- often only diagnosed at an advanced stage. The different types of dementia require different treatment, which in the case of Alzheimer's in particular is only effective at a very early stage. The medicines currently available are of no use when prescribed at an advanced stage, and treatment focuses largely on adapting the patient's living conditions and surroundings. As a result, feverish research is underway to find a way to diagnose Alzheimer's specifically, and to have reliable results even at an early stage.

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Zapaq, Inc. to Develop Drugs to Inhibit Beta-Amyloid Production

NEW YORK, NY--(INTERNET WIRE)--Jan 22, 2003 -- The Institute for the Study of Aging (ISOA) announced today that it has provided $250,000 in follow-on funding to Zapaq, Inc., a start-up biotechnology company dedicated to developing novel pharmaceuticals that inhibit a family of enzymes known as aspartic proteases, for the treatment of important human diseases, including Alzheimer's disease. The initial technology licensed into the Company was developed at the Oklahoma Medical Research Foundation and the University of Illinois.

Zapaq is headed by CEO James Jenson, Ph.D., who has served in senior positions with major pharmaceutical and biotechnology companies for more than 20 years. Zapaq's founding scientist, Jordan Tang, Ph.D., has played a leading role in determining the molecular structure of aspartic proteases. Dr. Tang pioneered a fundamental drug design element, the transition state analog, that is used in all marketed HIV-protease AIDS drugs today.

"The follow-on funding of Zapaq is consistent with ISOA's mission to fund the discovery and development of new therapeutics to prevent and treat Alzheimer's disease," stated Howard Fillit, M.D., Executive Director, ISOA. "We are proud to participate in the creation and continuing support of this exciting new biotechnology company. Jordan Tang is certainly an international leader in the development of aspartic protease inhibitors. With our initial funding, Zapaq has made significant progress in achieving preclinical proof of concept, and clinical trials are now on the horizon."

Zapaq is focusing on developing new compounds that block the formation or reduce the level of beta-amyloid. Dr. Tang has discovered a unique new aspartic protease (an enzyme also known as beta-secretase) called memapsin-2. His research is directed toward developing new compounds that target memapsin-2.

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Fat Intake Not Linked to Dementia Risk: Study
Mon Jan 20, 3:10 PM ET Add Health - Reuters to My Yahoo!

NEW YORK (Reuters Health) - Despite some hints that fat intake may affect the risk of dementia, a new study has failed to show a link between fats--both the "good" and "bad" types--and mental decline.

But the Dutch study is not the final word on the subject, its authors say.

It would be "premature" to conclude that cholesterol and fats that affect cholesterol are not related to the risk of dementia, according to a team led by Dr. M.M.B. Breteler at the Erasmus Medical Center in Rotterdam.

Several pieces of evidence suggest that fat and cholesterol may influence the risk of Alzheimer's disease (news - web sites) and other forms of dementia.

For example, animal studies have shown that a high-cholesterol diet increases the build-up of Alzheimer's-related brain proteins. In addition, some evidence suggests that cholesterol-lowering medications, including widely prescribed drugs called statins, may reduce the risk of Alzheimer's.

Also, a type of polyunsaturated fatty acid (PUFA) has been shown to battle inflammation. Since inflammation may increase the risk of dementia, these fatty acids, which are found in fish and fish oils, could conceivably cut dementia risk.

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Health - AP

Alzheimer's, New Cholesterol Gene Linked
1 hour, 56 minutes ago Add Health - AP to My Yahoo!

By LINDSEY TANNER, AP Medical Writer

CHICAGO - A variation in a gene that is supposed to help the brain break down cholesterol may play a role in some cases of Alzheimer's disease (news - web sites), researchers say.

A study found that people with this variant form face double the risk of developing late-onset Alzheimer's, the most common form of the disease. It typically develops after age 65.

The gene, called CYP46, is involved in production of an enzyme that helps break down excess cholesterol in the brain. The research suggests that the variation might hamper production of the enzyme, resulting in a buildup in the brain of cholesterol and a gummy protein called beta amyloid.

The research, though preliminary, fits in with growing evidence that elevated cholesterol levels may raise the risk of Alzheimer's.

It also adds to evidence that genetics are involved. Late-onset Alzheimer's already has been linked to another genetic variation in a different gene involved in helping transport cholesterol throughout the body. That variation is called APOE-4.

In the new study, patients with both the CYP46 and APOE-4 variants were almost 10 times more likely to develop the mind-robbing disease than those with neither variation. They also had the highest brain levels of beta amyloid.

Rest of article.

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AMPAkines
Alzheimer’s disease is characterized by progressive cognitive deficits, including learning and memory difficulties. Evidence indicates that the neurotransmitter glutamate plays an important role in learning and memory. In the hopes of enhancing cognition, compounds have been designed to positively modulate the AMPA subset of glutamate receptors. These centrally active drugs are called AMPAkines. Drugs that act at all glutamate receptors have limiting side effects such as excitotoxicity; however, this has not been a problem with specific AMPA receptor modulators.

Amyloid Deposit Modulators
Amyloid plaques (along with neurofibrillary tangles) in the brain are pathologic hallmarks of Alzheimer's disease. Families with inheritable, early-onset AD have been shown to possess a mutated form of the gene that encodes the amyloid precursor protein (APP), a protein that regulates the ability of b-amyloid to aggregate into plaques. The mutations generally have an effect on the processing of APP and the aggregation of b-amyloid, which, in turn, leads to AD pathology. The reasons for the deposition of b-amyloid in the late-onset form of AD are less clear; however, it is thought to be due, in part, to an increase in the production of b-amyloid and a reduction in its clearance.
To combat these abnormal states, drugs that inhibit amyloid deposition are in development. Prime therapeutic targets are the enzymes involved in the production of b-amyloid. Drugs called protease inhibitors work by blocking key enzymes involved in the formation of b-amyloid. Researchers also developed a vaccine to induce anti-b-amyloid antibodies that serve to reduce plaque formation, however some patients in phase II studies developed CNS inflammation with this vaccine, resulting in the cessation of clinical trials. Although these treatments are still in early clinical trials, they are exciting prospects for future treatment.

Anti-inflammatory Drugs
Proteins associated with the inflammatory response, as well as activated microglia, are abundant in the brains of patients with Alzheimer’s disease (AD). This inflammatory response may contribute to the pathology of Alzheimer’s disease. These proteins include a-1-antichymotrypsin, cytokines, and complement proteins, among others. Evidence is mounting that b-amyloid itself, a protein thought to contribute to AD pathogenesis, might induce the inflammatory response.
Clinical evidence suggests that people using anti-inflammatory agents, particularly NSAIDs, for extended periods have a lower probability of developing AD. It has been suggested that NSAIDs called cyclooxygenase (Cox) inhibitors may be particularly important in Alzheimer’s disease. This is based on evidence that the Cox inflammatory protein is highly expressed in the brains of Alzheimer’s disease patients. Researchers believe that blocking the action of this protein may slow down the brain damage caused by inflammation. Several drugs including are in trials to test this hypothesis.
Recently, a large retrospective study was published in the New England Journal of Medicine, that supported the possible role of NSAIDs in preventing Alzheimer's disease.
Dr. in’t Veld and colleagues looked at 6989 patients in a suburb of Rotterdam, in the Netherlands. These patients were aged 55 years and older and had no evidence of dementia. They were followed for an average of 6.8 years and their use of NSAIDs were monitored by reviewing pharmacy prescriptions (prior to 1995 NSAIDs were available only by prescription in the Netherlands). They found that patients that used NSAIDs for more than two years of cumulative use had an 80% reduction of risk of developing Alzheimer’s disease. For those who used NSAIDs for more than 1 month but less than 24 months, the risk was reduced by 17%, and for those who used NSAIDs for less than 1 month, the risk was only reduced by 5%. Interestingly, as seen in previous work, the reduction of risk was seen at low doses of NSAIDs as well as higher doses. They found no association between use of aspirin and risk of Alzheimer’s disease.
It should be noted that much of the available data are indirect and more evidence is needed before conclusions can be drawn about the effects of anti-inflammatory agents on the course of AD. Furthermore, there are risks associated with the use of long term NSAID use, including the risk of GI bleed, which can be serious or even life-threatening.

Anti-oxidants
Oxidative molecules are present in the brain of patients with Alzheimer’s disease (AD). Several possible sources of these oxidative moieties have been suggested. It is hypothesized that b-amyloid, a protein thought to play a key role in the pathogenesis of AD, as well as elevated levels of iron, induces free-radical production. Additionally, the inflammatory response that occurs in AD patients generates many potent oxidants (e.g., nitric oxide molecules). There are several compounds currently available or under study that may function as free-oxygen radical scavengers, notably selegiline, vitamin E, and the plant extract ginkgo biloba.
Vitamin E has been studied in the past with some questionable benefit, although results have not been conclusive. Because of the favorable side effect profile, however, many clinicians prescribe vitamin E for their Alzheimer’s patients with the hope that it will provide some benefit. Now, a more recent study published in the Journal of the American Medical Association (JAMA) supports the claim that antioxidants may reduce the risk of Alzheimer’s disease.
Engelhart and colleagues (1) examined a total of 5395 participants, who were part of The Rotterdam Study in the Netherlands. These patients at baseline were at least 55 years old and free of dementia. They were monitored for a mean of 6 years, and 146 developed Alzheimer’s disease. The researchers monitored their diet and vitamin supplement intake closely. They then accounted for various confounding factors including smoking, age, sex, baseline Mini-Mental State Examination score, education, alcohol intake, body mass index, presence of carotid plaques, and use of antioxidant supplements. When these factors were adjusted for, they found that high intake of vitamin C and vitamin E was associated with a reduced risk of Alzheimer’s disease of about 18% (per standard deviation increase in intake of these vitamins). This reduction of risk was even more pronounced in reducing the normally increased risk of Alzheimer’s disease in smokers, which the authors of this study suggest may in part be due to the antioxidant effect on reducing the increased load of free radicals caused by smoking.
Controlled studies, however, are still lacking and the benefit of antioxidants in Alzheimer’s disease is still not conclusive. This study may also inspire further research, including hopefully investigation into the mechanism by which antioxidants seem to affect the process of Alzheimer’s disease. While these vitamins are available over the counter, they do have some side-effects, particularly at higher doses, and individuals should discuss with their doctor whether these vitamins are right for them before taking them regularly.

Cholinergic Agonist
Cholinergic agonists, also known as muscarinic and nicotinic agonists, are still in the early stages of development. These drugs are designed to improve cognitive ability in Alzheimer's disease patients by mimicking acetylcholine activity (i.e., stimulating specific receptors within the synapse). So far, studies of the cholinergic agonists have not demonstrated that they impart a greater effect on cognitive abilities than the cholinesterase inhibitors. Additionally, peripheral adverse reactions are prominent, including gastrointestinal side effects and syncope. However, there appears to be a reduction in some troublesome behaviors such as agitation, delusions, and hallucinations. Several new cholinergic agonists with lower toxicity and greater specificity to central nervous system receptors (as opposed to peripheral receptors) are being tested.

Cholinergic Precursors
Therapeutic strategies to augment the concentration of cerebral acetylcholine with cholinergic precursors are being evaluated in Alzheimer’s disease (AD). They are a logical step in the treatment of AD, although many studies have not produced clinically significant results. Clinical trials with lecithin have been inconsistent although a single study reported significant improvement in learning and memory in older patients when they were administered low doses of the drug. Combination therapy with tacrine, a cholinesterase inhibitor, did not reveal any additive effects. A more promising prospect is CDP-choline. A number of studies have consistently reported positive effects with CDP-choline in patients with dementia. However, these results may be due, in part, to a membrane stabilization effect.

Cholinesterase Inhibitors
The first significant advance in the treatment of Alzheimer's disease (AD) was the development of agents for enhancing the availability of acetylcholine by inhibiting the enzyme, cholinesterase, which breaks down this neurotransmitter. The premise is that by blocking cholinesterase, acetylcholine levels will be elevated within the synapse, thereby improving the AD patient’s cognitive ability (i.e., memory, attention span and concentration). These medications appear to primarily provide symptomatic improvement in memory and cognition. However, recently there is data to suggest they may also slow the progression of the illness somewhat, although the mechanism behind this is not clear.
Acetylcholinesterase inhibitors are the most common approach to treatment of the cognitive symptoms of AD. Tacrine, donepezil, rivastigmine, and galantamine are currently approved cholinesterase inhibitors. Tacrine is rarely used anymore due to to side effects and the need for blood monitoring. Several other cholinesterase inhibitors are being developed that vary in specificity and duration of action and their affinity for cholinesterase. Further clinical study is needed to determine if there is any difference in efficacy between these medications.
The major adverse reactions associated with cholinesterase inhibitors are related to the peripheral cholinergic effects. These include nausea, vomiting, diarrhea, muscle cramping, and fatigue, but they tend to be mild in intensity, short in duration and resolve without discontinuing treatment. Tacrine, however, has the unique feature of causing reversible elevations of liver enzymes that may need close monitoring in patients taking the drug.

Ergot Alkaloids
Alzheimer’s disease (AD) was once considered to be a vascular disease and the vasodilatory ergot alkaloids were marketed as potential AD drugs. Recent molecular research does not support this premise and many of the ergoloid mesylates such as hydergine have been set aside, at least in the United States, in favor of cholinesterase inhibitors. In Europe, however, hydergine is one of the most commonly prescribed drugs for cognitive enhancement in the elderly. Its mechanism of action is not well understood, but it has complex actions on central a-adrenergic, dopamine, and serotonin receptors. It also has been classified as a metabolic enhancer due to its action on cyclic AMP. Many studies have been conducted on the ergot alkaloids and evidence is accumulating in favor of their use as cognitive enhancers when taken at high doses. Side effects are unpredictable but may include stomach upset and temporary nausea.

Estrogens
Investigation of estrogen replacement therapy (ERT) as a treatment for Alzheimer’s disease (AD) has focused primarily on postmenopausal women. Regardless, the evidence is strong that ERT influences central nervous system function. It is known to enhance the function of cholinergic neurons, the cells most heavily damaged in AD. It has several other neurotrophic functions, such as enhancement of acetylcholine synthesis and a possible decrease in cerebral amyloid deposition--two functions that make ERT a logical AD treatment. One study demonstrated that estrogen might augment the neurotransmitter effects of tacrine, a cholinesterase inhibitor approved for use in AD treatment. Three large prospective epidemiologic studies have suggested that postmenopausal women who used estrogen had not only a reduced risk of developing AD but also had a later age of diagnosis compared to women who never used estrogen. However, recent studies have reported conflicting results and have raised some doubt about estrogen's protective effect against AD. Studies of estrogen as a treatment for AD (rather than as a preventive agent) have been mostly negative. Some possible negative aspects of ERT include a potentially elevated risk of uterine and breast cancer. At present, the data are insufficient to recommend ERT as a treatment option for AD; however, clinical trials continue to test ERT as a possible therapy or preventative measure in AD.

NMDA Receptor Agents
N-methyl-D-aspartate (NMDA) receptors are stimulated by glutamate and are important in the formation of memory. These receptors appear be reduced in Alzheimer's disease (AD). Additionally, some evidence suggests that excessive activation of NMDA receptors may contribute to the degeneration of cholinergic cells. Several drugs have been studied that either enhance or antagonize NMDA receptors. The role and mechanism of NMDA receptors in memory is complicated, and the most effective way to pharmacologically manipulate these receptors to improve memory is unclear. However, the best studied of these agents are the NMDA antagonists. Memantine, an NMDA antagonist, has been approved for use in Europe and is awaiting FDA approval for use in moderate to severe Alzheimer's disease in the USA. Phase III studies suggested it was superior to placebo in these patients, and fairly well tolerated.

Neotrophic Agents
The survival of cholinergic neurons in the basal forebrain is dependent on nerve growth factor (NGF) and animal studies indicate that it counteracts neuronal atrophy. Since the cholinergic neurons are severely affected in Alzheimer’s disease (AD) therapy with NGF and other growth factors might be beneficial. Very few studies have been conducted on the efficacy of this type of treatment, likely because administration of the drugs is difficult. NGF does not cross the blood-brain barrier and requires either carrier molecules or intrathecal delivery. Clinical trials conducted in Europe have met with limited success, but leteprinim potassium, marketed as a nootropic, has been reported to stimulate production of NGF and is currently in clinical trials in the United States. Still, further research is needed to determine the usefulness of this type of therapy for AD patients.

Nootropics
Nootropics are agents that enhance memory and learning by directly affecting brain function and metabolism. The mechanism for improved cognition in Alzheimer’s disease (AD) has not been established although it is believed that they may enhance CNS microcirculation. The nootropics are primarily being developed and marketed for dementia and cognitive impairment in countries other than the United States. However, two drugs, indeloxazine and leteprinim potassium, are currently undergoing clinical trials for AD in the US, and both may have potential for conferring moderate neuroprotection. The data from clinical trials are still unclear.

Protein Kinase Inhibitors
Protein kinases are generally involved in a number of important cellular pathways. Of particular relevance to Alzheimer’s disease, the cellular pathway leading to apoptosis or programmed cell death is mediated in part by protein kinases. Since Alzheimer’s disease is characterized by neuronal cell death, inhibiting apoptotic pathways via targeting of protein kinases is one strategy being employed to avert neurodegeneration and slow the progression of the disease. Early clinical studies in Alzheimer’s disease patients are underway to test this novel therapy.

Statins
Recent studies have suggested that the statin class of drugs (lovastatin, pravastatin, etc.), may lower the risk of AD. Statins lower cholesterol levels by inhibiting an enzyme needed for cholesterol synthesis.
A study in theArchives of Neurology found that in a cross-sectional analysis of hospital records, patients taking statins had a 60 to 73% lower prevalence of Alzheimer’s disease during their study interval. In another epidemiologic study in a recent edition of the Lancet, researchers found the relative risk of developing dementia was lower (0.29) in patients taking statins. In this latter study, other risk factors such as age, coronary artery disease, smoking, etc., were adjusted for. However this study included all types of dementia, not only Alzheimer’s disease. Interestingly, patients taking non-statin lipid lowering agents did not have a reduced risk of developing dementia in this study.
These studies suggest that statins may have a role in prevention of dementia. However, both of these studies are retrospective, and placebo-controlled, double-blind studies are necessary before definitive conclusions can be drawn. There is evidence to suggest a relationship between lipids and different forms of dementia. These studies are one step in trying to determine what that relationship is, and how it can be used to prevent and treat Alzheimer’s disease.

Put together from the Veritas site. Signing up with this site will give you the option of receiving up to date clinical trial and/or research information by email.

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Hospital Costs Similar, Despite Alzheimer's Gene
1 hour, 33 minutes ago

By Alison McCook

NEW YORK (Reuters Health) - People enrolled in Medicare who carry a genetic variation known to increase the risk of Alzheimer's disease (news - web sites), heart disease and stroke appear to incur no more hospital costs than other elderly patients who are hospitalized, US researchers report.

About a quarter of the population inherits one or two copies of the gene, known as APOE-e4, from their parents.

Currently, neither private insurers nor Medicare makes financial decisions based on whether or not their clients carry this genetic variation, but the current study suggests they never should, Dr. Donald H. Taylor, Jr. of Duke University in Durham, North Carolina told Reuters Health.

Some health maintenance organizations (HMOs) cover a percentage of people enrolled in the government health program Medicare. These private companies have a "great interest" in learning how to estimate the health care costs associated with different enrollees, in order to determine how much to charge Medicare for their service, said Taylor.

"Our study gives caution that the (genetic variation) does not predict hospital costs well, so it does not appear to be a good candidate for this purpose," he said.

The APOE gene, which codes for a cholesterol-carrying molecule, comes in three versions: e2, e3 and e4.

Previous research has shown that people with one or two copies of APOE-e4 (from one or both parents) are at greater risk of developing Alzheimer's disease, heart disease and stroke than those with a different combination of the genes. About a quarter of the population has one copy of APOE-e4, while about 2% have two copies.

Currently, tests to determine if a person carries this genetic variation are not routinely performed in the general population.

Approximately one third of the participants in the current study carried APOE-e4.

SOURCE: American Journal of Geriatric Psychiatry 2003;11:75-82.

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Thursday, 9 January, 2003, 07:01 GMT
Researchers tackle age-related diseases

Scientists hope to prevent conditions like Alzheimer's

A new company which will develop treatments for age-related diseases such as Alzheimer's is to be set up in Manchester.
Senexis, based at the city's UMIST university, will aim to create new drug treatments to tackle degenerative brain conditions.

The new company will operate with £1.4m of funding.

Parkinson's Disease, CJD and motor-neurone disease are other examples of illnesses which are caused by these conditions.

Scientists believe they are all caused by a condition called amyloidosis whereby specific proteins stick together to form toxic groups which kill brain cells.

Article

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Interleukin's Good Side
17 minutes ago Add Health - HealthScoutNews to My Yahoo!

FRIDAY, Jan. 10 (HealthScoutNews) -- Mayo Clinic researchers have found the hormone interleukin-6 protects brain cells in mice, a finding that may hold promise for humans as well.

The good news comes from a study in the Jan. 15 issue of the Journal of Neuroscience.

Interleukin-6 (IL-6) is found inside cells. The hormone is often regarded as a negative player in the immune system because of its association with inflammation injuries and malignant diseases. However, this study says Il-6 protects brain cells in mice.

The researchers studied different groups of mice that were genetically engineered to have variations in their ability to produce IL-6. All the groups of mice were injected with a virus that causes a degenerative nerve disease.

Of the 23 infected mice with the IL-6 gene, two died. In the infected mice that lacked the IL-6 gene, 17 of 29 died.

When they examined the mice, the Mayo Clinic scientists found dramatic degeneration of neurons in the spinal cords of the mice without the IL-6 gene. When they examined the brains of the mice with the IL-6 gene, they found IL-6 everywhere in the mouse brains.

That surprised them because IL-6 isn't found in brains of healthy animals.

In the mouse brains, IL-6 was found in astrocytes, which are supporting structures on the outside of brain cells that help connect the brain cells to transmit nerve signals. The researchers say the astrocytes in the mouse brains started making IL-6 after the mice were infected with the virus.

Identifying factors that protect brain cells may help find ways to fight diseases such as Alzheimer's disease (news - web sites) and Parkinson's disease (news - web sites).

Article

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09 January 2003

ChI benefits extend beyond memory in AD
Cholinesterase inhibitors (ChIs) used to preserve memory and intelligence in people with Alzheimer's disease (AD) may also have a beneficial impact on neuropsychiatric and functional outcomes in these patients, researchers reveal.

Although memory loss is the symptom most commonly associated with AD, Nhi-Ha Trinh (Massachusetts General Hospital, Boston, USA) and colleagues note that "as many as 80% of patients with AD will experience neuropsychiatric symptoms such as hallucinations, paranoia, agitation, and affective disturbances during the course of their illness."

In addition, functional impairment, which occurs in all patients, can lead to individuals being unable to maintain their daily activities.

To ascertain the effect of ChIs on these significant symptoms, the team carried out a literature review and identified 29 clinical trials involving outpatients diagnosed with mild-to-moderate AD who received treatment with a ChI for at least 1 month.

The effect of ChIs on neuropsychiatric outcomes was assessed using the Alzheimer Disease Assessment Scale-Noncognitive in 10 trials and revealed that, compared with placebo, the drug improved patients scores by 0.03 points.

In six trials that used the Neuropsychiatric Inventory, patients randomly assigned to ChIs showed a 1.72 improvement in scores over those obtained with placebo.

In the case of functional outcomes, 14 trials using the Activities of Daily Living scale demonstrated an improvement in scores of 0.1 with ChIs compared with placebo, while, in 13 trials, scores on the Instrumental Activities of Daily Living scale improved by 0.09.

"Our data suggest that for patients with mild-to-moderate AD who have neuropsychiatric disturbances, ChIs should be considered a therapeutic option," says the team in the Journal of the American Medical Association.

"Future research should focus on how such improvements translate into long-term outcomes, such as patient quality of life, institutionalization, and caregiver burden."

JAMA 2003; 289: 210–216

Comes out of the same research as the one a couple of posts down. Abstract of the study here.

The articles make sense of some things for me. I, like others, noticed a definite difference in Mom when she started on Aricept, several years ago now. There were 3 "events" in particular.
1)There was one day we were coming home from somewhere, and it occured to her for the first time in a long time, to get the remote from the glove compartment to open the garage door!
2)I was setting up the coffee pot for the morning. From another room, where she couldn't see what I was doing, she said "sounds like someone is fixing the coffee"! That's rather abstract thinking, vs concrete, since she couldn't actually see what I was doing, and all abstract thought had been long gone by then.
3) ..... ummmmm, I can't remember Damn it! Imagine that

The differences that came, went after about 6 months, and in the readings, that's fairly typical, 6 months to a year. But I've never stopped, and won't stop, her Aricept. Reason being, I've known people that have stopped their LO's Aricept, or the doc has, after the improvements faded. And in the majority of those, there were dramatic "downslides" in their LO's condition, in more than just one "area", not regained in those that restarted the Aricept. Once it was gone, it was gone. These are the things that really make more sense to me, now, reading this information. It really does.

Granted, my unwillingness to stop her Aricept has excluded her from some clinical studies, and likely will in the future. And maybe that "stubborness" on my part has stopped her from getting some benefits she may have otherwise had. But the fear of that potential "downslide" just stops me cold. I lose enough of her each day in little pieces. And these studies
rather "qualify" my reasons, to myself, for doing as I've done, and make sense of them.

So many decisions, so few destructions

ces

i to noticed a vast improvement with rob when he started taking aricept. it really does hold the effect of ad off. as his dr. said he's able to think much more then before the aricept.

StemCells, Inc. News Release - 8-Jan-2003

U.S. Patent Office grants StemCells, Inc. 3 neural stem cell patents, including first patent for transplantation of human neural stem cells.

Palo Alto, California, January 8, 2003/PR Newswire/ – StemCells, Inc.
announced today that the U.S. Patent office has granted U.S. Patent Number 6,497,872 with broad claims covering the transplantation of mammalian tissue–derived neural stem cells and their progeny into the central nervous system (CNS) and the peripheral nervous system including the spinal cord. The patent, of which StemCells is the exclusive licensee, also covers transplantation of cells derived from neural stem cells and genetically altered cells. In addition, U.S. Patent Number 6,498,018 for drug screening using human neural stem cell cultures and Number 6,468,794 covering methods for producing a cell population enriched for neural stem cells that can initiate neurospheres, have recently been issued to the Company.

“The issuance of U.S. Patent 6,497,872 is an extremely important event for StemCells, Inc. It is the first patent to be issued anywhere in the world with claims covering transplantation uses of human neural stem cells,” said Martin McGlynn, President and CEO of StemCells Inc. “The claims cover the transplantation of neural stem cells themselves as well as neurons or glial cells derived from the stem cells; thus, for example, transplantation of stem cells or neurons derived from neural stem cells for the treatment of diseases such as Parkinson’s, Alzheimer’s, stroke or spinal cord injury would be subject to the claims of this patent irrespective of the culture method used to grow the cells. Moreover, the claims cover both normal and genetically modified neural cells, so the patent also covers gene therapy applications using neural stem cells. We view the grant of patent number 6,498,018 as having the potential to broaden the Company’s future product range to include drug screening as well as disease treatment, and patent number 6,468,794 as protecting the Company’s position in respect to commercially feasible methods for producing therapeutic numbers of vigorous neural stem cells.”

The issuance of these patents adds to StemCells, Inc.’s portfolio of more than 30 issued patents in the neural stem cell field, enhancing the Company’s position in the therapeutic, diagnostic, genomics and drug discovery uses of neural stem cells.

StemCells, Inc is a biotechnology company focused on the discovery, development and commercialization of stem cell-based therapies to treat diseases of the nervous system, liver, and pancreas. The Company’s stem cell programs seek to repair or repopulate neural or other tissue that has been damaged or lost as a result of disease or injury. Further information about the Company is available on its web site, at www.stemcellsinc.com

Rest here.

Anyone interested, here is U.S. Patent Number 6,497,872 And it's LONG! But there's a LOT of information and explanations after the list of references.

While one may not like the "business" end of that article, we must bear in mind that in the US we have a free enterprise system, and it is the free enterprise system that is responsible for most of the advances in modern medicine. The only way companies can protect themselves and profit from their research is to make their findings proprietary, which includes patents. Patents don't normally deter research but stimulate it.

ces