Alzheimer Related News Items
News as of 11/09/98
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Top Items
Scientists Cultivate Cells at Root of Human Life - Scientists have for the first time picked out and cultivated the primordial human cells from which an entire individual is created. Two forms of human embryonic stem cells have been developed, one by a team under Dr. James A. Thomson of the University of Wisconsin in Madison, the other by Dr. John Gearhart and colleagues at the Johns Hopkins University School of Medicine in Baltimore, Md. The work was funded by the Geron Corporation of Menlo Park, CA because Federal law will not fund this type of research. Dr. Thomson grew his embryonic stem cells from the inner cell mass of blastocysts that had been left over from fertility treatments and were due to be discarded. Dr. Gearhart's group has developed embryonic stem cells from the germ cells of aborted fetuses. The cells developed by the two groups may well be equivalent, but this has yet to be proved. Eventually, researchers hope to use the cells to grow tissue for human transplants and introduce genes into the body to remedy inherited disease such as Parkinson's disease and by analogy AD. As to the ethical issue Dr. Gearhart said he did not consider the cells that he and Dr. Thomson have isolated to have a special moral status because "they cannot form a fetus -- you cannot take one of these cells and form a being out of it." Embyronic stem cells are also immortal because, until they become committed to specialized fates, their telomeres are renewed each time they divide. Unlike ordinary cells, they grow indefinitely in culture. NY Times 11/6/98 by Nicholas Wade and Wash Post 11/6/98 by Rick Weiss with Thomson's work in Science 1998 282:1145-47 and Gearhart's work in Proceeding of the National Academy of Sciences 95:13726-13731 (Nov. 10)

Doctors Regenerate Human Brain Cells - Doctors at the Salk Institute for Biological Studies in La Jolla, CA and at the Sahlgrenska University Hospital in Sweden have shown, for the first time, that human brain cells do divide and grow -- something that opens great possibilities for treating brain damage caused by accidents and disease. Conventional wisdom has held that the human brain is special -- that the neurons and other cells do not grow and divide like other cells and that this is why brain damage is so hard to correct. These doctors were looking for evidence that human brain cells grow, naturally, in the brain. They looked at the brains of terminal cancer patients who had been treated with a chemical, bromodeoxyuridine, (BrdU) that is sometimes used to mark rapidly dividing cancer cells. They found that the chemical had been taken up by the DNA in the hippocampus, which is involved in learning and memory. Their study demonstrates that cell genesis occurs in human brains and that the human brain retains the potential for self-renewal throughout life. Although the hippocampus is one small area of the cerebral cortex where a vast number of brain functions occur, it is the area where cell loss occurs in AD patients, so its importance is real. Why this disease, and other neurological disorders, would occur despite the creation of new neurons replacing the old is one of the many questions now to be investigated. Reuters 11/3/98 by Maggie Fox, Health and Science Correspondent and NYT 10/30/98 by Holcomb B. Noble. In Nature Medicine vol. 4, No. 11 1313-13127 (Nov. 98)

Tau Gene Linked to Family of Neurodegenerative Disorders; Finding May Yield Insight Into Onset of AD - Researchers at UC San Francisco have identified three mutations in a
gene that produces the tau protein, and have determined that these mutations cause several related hereditary neurodegenerative diseases, the most prevalent known as frontotemporal lobe dementia. While the finding does not directly implicate the tau gene in AD, it does so strongly by association. Previously researchers had never found a mutation in the tau gene of AD patients and they had come to think that the neurofibrillary tangles, composed primarily of tau protein, were but an inconsequential by-product of some other factor that actually caused nerve cell degeneration. Now that there is hard evidence that tau, itself, is capable of killing brain cells, the picture changes. Finding a direct link between mutations in the tau gene and these hereditary neurodegenerative diseases strongly indicates that tau is an important player in neurons dying in AD and many other diseases, as well. The goal now is to figure out what causes tau protein to accumulate in insoluble filaments in the brain cells of AD patients. PR 10/26/98 Proceedings of the National Academy of Sciences 95:13103-13107 10/27/98

Drugs
SIBIA Neurosciences Announces Issuance of U. S. Patents - U.S. Patent No. 5,804,560, relates to using certain of SIBIA's proprietary compounds for the treatment of central nervous system disorders involving cerebral amyloid deposits, and includes possible future therapies for AD. The other three, U.S. Patent Nos. 5,792,846, 5,801,232 and 5,807,689, relate to assay methods for screening compounds to identify drug candidates with potential for treating pain, dementia, anxiety, schizophrenia, depression and stroke. The assay methods involve proprietary classes of human ion channels (voltage-gated calcium channels, nicotinic cholinergic channels, and metabotropic glutamate receptors) expressed in neuronal cells by SIBIA. PR 10/12/98

New FDA Ruling Expands Aspirin's Cardiovascular Uses - The FDA has broaden the professional labeling for aspirin for expanded uses to include: use during acute MI; expanded use for stroke prevention; use for high risk individuals to include prevention of heart attack and stroke; and use of lower dosages for heart attack and stroke prevention. Often described as a ``wonder drug,'' aspirin is currently the subject of numerous ongoing research studies involving prevention of AD and several forms of cancer, including colon cancer, and treatment of migraine headaches. PR 10/21/98

The Double Whammy Drugs - Treatment with the antihypertensive drug nitrendipine to bring down high blood pressure in elderly people also reduces the risk of dementia. High blood pressure is known to be the strongest risk factor for dementia in elderly people. Their mental ability was then assessed using a test known as the "mini mental state examination," which measures recall, short term memory, attention and ability to calculate. The incidence of dementia among patients who received drug therapy fell by 50% compared with patients who were not treated from 7.7 to 3.7 cases per 1,000 patient years. This means that if a 1,000 hypertensive patients were treated with antihypertensive drugs for five years, an estimated 19 cases of dementia would be prevented. It is thought that antihypertensive drugs may protect against dementia because they improve blood flow to the brain, but nitrendipine may have a direct effect on the brain. BBC News 10/23/98

A Cigarette Chemical Packed With Helpful Effects? - Nicotine is being studied as a possible therapy for a broad range of ailments that includes AD and Parkinson's diseases, schizophrenia, depression, adult attention deficit disorder, Tourette's syndrome and ulcerative colitis. Additional research is developing drugs that mimic nicotine's positive effects, but don't produce its negative side effects. At the annual Society for Neuroscience meeting work on nicotine and nicotine-like drugs was reported. Edward Levin and colleagues at Duke University have a nicotine-like compound, AR-R 17779, that appears to improve learning and memory in rats. Levin focuses on what are known as "alpha-7 nicotinic receptors," which are found in great concentrations in the hippocampus, part of the brain important to memory and learning. Receptors are cellular locks that wait for a chemical with a specific shape to act like a key and trigger functions within the cell. In nicotinic receptors, nicotine fits the locks meant for acetylcholine (ACh), one of the body's natural receptor keys. When rats were injected with the chemical, they ran mazes more effectively. When given to rats whose memories had been impaired by damaging pathways to the hippocampus, those rats improved as well. This is a hopeful sign for AD research because the connection to the hippocampus is often damaged in AD victims. Researchers at R. J. Reynolds have found similarly encouraging results with their nicotine mimics known as RJR-2557 and RJR-1734, which also trigger the brain's ACh receptors. Patrick Lippiello gave the drugs to rats and found that the compounds boosted short-term and long-term memory. The effects last about 18 hours in rats, the drugs can be taken orally, and it seems to protect rat brain cells from being destroyed by some toxins, which could point the way to a therapy that not only alleviates the symptoms of AD, but also prevents brain cell degeneration. Since you can only trigger receptors if there are receptors to be triggered, the drug, if effective in humans, will best be used if the disease can be caught in the early stages. By John Schwartz Washington Post 11/9/98

New Computerized Processes Slash the Time It Takes to Develop New Chemical Compounds- A new report from Technical Insights/John Wiley entitled ``Directions in Combinatorial Chemistry: Speeding Compounds to Market'' investigates the current state-of-the-art in combinatorial chemistry. Using parallel processors and powerful data
management and screening software, combinatorial chemistry offers a method for rapidly
synthesizing millions of new compounds that have potential value. Case histories of successful applications of this technology in human genome research, AD treatments, immunology, luminescent materials research, and more are given. PR 10/9/98

Genes & Genetic Issues
Stem Cells Expected to Help Neurological Research - Researchers isolated neural stem cells (NSCs) from human fetal tissue to combat neurodegenerative diseases, according to two studies in the November issue of Nature Biotechnology. Previously, these types of cells had only been isolated from rodents. Neural stem cells give rise to more specialized cells of the central nervous system. These cells, found in developing or degenerating regions of the central nervous system, are able to differentiate into a variety of cell types. The stem cells "could ultimately be used in cell replacement and gene therapies for patients with neurodegenerative disease or paralysis," according to a statement from the journal editors. The two teams of researchers are Dr. Jonathan D. Flax of Harvard Medical School in Boston, MA and Oliver Brustle and colleagues with the National Institutes of Health, the University of Bonn Medical Center in Germany and the Institute Pasteur in France. Reuters 11/3/98 Nature Biotechnology Nov. 1998

Many Fear Loss of Privacy after Gene Testing - With 1,170 New York residents interviewed last month by Yeshiva University researchers regarding their views on genetic testing, over two-thirds (69%) of all respondents said they would welcome the chance to take a test determining their genetic risks of treatable diseases like cancer or heart disease. A somewhat smaller percentage (59%) say they would also undergo testing for disorders like AD for which there is currently no effective treatment. However, 90% of those polled said they were either very concerned or somewhat concerned that information derived from genetic tests might be made available to third parties and they worry that those test results could be divulged to others, such as employers and health insurance companies. Reuters 10/12/98

Parkinson's Gene Mutation Explored - Researchers at the Harvard Medical School have discovered how a gene mutation associated with an early-onset familial form of Parkinson's disease kills nerve cells in the brain. Apparently, the abnormal protein causes other proteins to aggregate, and these deposits kill nerve cells. The finding may lead to new treatments for Parkinson's disease, and may also lead to new treatments for AD. The mutation in question is in the gene that produces alpha-synuclein, a compound found in Lewy bodies -- fibrous deposits found in the dopamine-producing nerve cells of the brains of patients with Parkinson's disease. When a mutant type of alpha-synuclein, A53T, was concentrated and encouraged to aggregate, it formed fibrils characteristic of Lewy bodies more quickly than did the normal alpha-synuclein or another mutant form, A30P. The researchers want to make a drug and target it toward inhibiting fibril formation. If you could delay the age of onset of Parkinson's disease by approximately 20 years, that would be a de facto cure. Early-onset Parkinson's disease is similar to early-onset AD in that genetic mutations seem to accelerate the development of the disease. Significantly, the prevalence of AD in the Parkinson's disease population, and vice versa, is far greater than would be expected by chance. This observation is consistent with the notion that both diseases arise from similar processes and could be treated by similar strategies. Reuters 11/4/98 Nature Medicine 1998;4:1318-1320

Human Genome, Half Completed, Posted on Web - Researchers have unveiled an updated map of the human genome -- the human genetic blueprint -- that includes about half of the body's estimated 60,000 genes. It is published on the Internet this week, at www.ncbi.nlm.nih.gov/genemap , and the map includes nearly twice as many genes as an earlier version published in 1996. Among other things, the updated map should help researchers find genes that, when mutated, cause hereditary disease. This research, in turn, could help scientists find new genetic tests and treatments for these and other illnesses and health problems. Since the genome project was launched in 1994, scientists have found mutations that play roles in numerous diseases and health problems, including cystic fibrosis, obesity, AD and Parkinson's diseases, and various cancers. Reuters 10/23/98 Science 1998; 282:744-746

Controlled Cell Death - Cell death, also known as apoptosis, is vital for an organism. The death of nerve cells in certain forms of AD and also possibly the damage done to the brain after a stroke are the result of too much apoptosis. Scientists at the Max Planck Institute of Biophysical Chemistry have shed light upon the function of the gene which acts as a switch in the chain of the molecular process and which leads to the death of a cell. This gene, Apaf1 (Apoptotic protease activating factor 1) plays a central role in programmed cell death in mammals. Apaf1, as a key component of apoptosis, could become a very attractive object for many areas of medical research, for the development of new anti-cancer strategies, the treatment of neurodegenerative diseases (AD) and other genetic diseases, which involve a malfunction of the apoptosis pathway. PR 10/8/98 Cell, Vol. 94: 727-737, 10/18/98

Caregivers
AD: Severity at Onset Important - Severity of disease at initial evaluation, and not rate of cognitive decline, is a more accurate predictor of AD patient outcomes, according to a study at the University of Massachusetts School of Medicine presented at a meeting of the American Neurological Assn. The disease progression of 98 AD patients for an average of nearly 55 months. They compared various factors, including severity at entry and 12-month functional and cognitive decline, to endpoints of dependence in self-care, institutionalization, and death. The researchers report that none of the end points examined was predicted by rate of cognitive decline. The dependence in self-care was best predicted by signs on initial visit and cognitive score at 12 months, but not by rate of cognitive or functional decline. Institutionalization was best predicted by incontinence and rate of functional decline, but, again, not by the rate of cognitive decline. Reuters 10/21/98

Testing
Noninvasive Test Detects AD - A scanning technology called near-infrared fluorescent spectroscopy could form a basis for the noninvasive diagnosis of AD in living patients according to researchers at the Bedford Veteran's Administration Medical in Bedford MA. The near-infrared end of the light spectrum passes easily and harmlessly through the bones of the skull. Once these rays penetrate the brain itself, they reflect back wavelength patterns corresponding to each type of tissue encountered. The researchers have tested the technology on post-mortem tissue samples taken from the brains of both healthy and AD patients and discovered very clear differences between fluoroscopy patterns produced by both types of tissues and in blinded studies they had a near-100% accuracy rate in diagnosing AD-affected tissues. The researchers plan to study the use of near-infrared fluorescent spectroscopy in the diagnosis of living patients and if successful, the technology might be available for clinical use within 3 to 5 years. The researchers note that although there are no effective treatments for cases of advanced AD, early detection may allow initiation of treatment designed to slow the progression of AD. There's some evidence now that oxidative damage or inflammatory changes may be important, and if you could detect someone very early and start treating them, you would have a good chance of having a good outcome. Reuters 10/19/98

Elevated Homocysteine Levels a Possible Risk Factor for AD - Dr. A. David Smith of the University of Oxford, UK, presented his group's findings that elevated homocysteine levels are associated with histologically AD and vascular dementia. Serum total homocysteine levels were significantly higher and serum folate and vitamin B12 levels were significantly lower in patients with the disease than in 108 controls. Dr. Smith said "our hypothesis was that there is a vascular trigger for AD. Our results are consistent with this, but it doesn't mean that this is proof." In an editorial accompanying the AMA Archives of Neurology article, it is suggested that neurologists may want to add measurement of homocysteine levels to the routine battery of tests for patients with dementia. Reuters 10/19/98 Arch Neurol 1998;55:1449 (11/98)

Competitive Technologies, Inc. (CCT) Reports Homocysteine Updates - CTT has patents on any assay used to determine if an individual has an elevated homocysteine level and a corres- ponding deficiency in folate or vitamin B12. The increase in the number of assays performed by its third party licensees reflects the growing attribution of the importance of homocysteine as a measurable risk factor for coronary artery disease, the leading cause of death in the United States. In addition to the implications of homocysteine and coronary artery disease, new studies are also indicating that there may be a relationship between elevated levels of homocysteine and conditions such as AD, Chronic Fatigue Syndrome and Rheumatoid Arthritis. PR 10/9/98

Prevention
Two-Thirds of American Women Age 40 and Over Don't Know Much About Sex Hormones - The vast majority of women entering menopause could benefit from taking hormone replacement therapy (HRT), yet fewer than 25% of these women are actually doing so. Much of this can be attributed to the lack of awareness about the health role that hormones play for women, especially as they reach menopause. As a woman enters menopause, levels of naturally-produced estrogen and progesterone drop sharply, often causing hot flashes, mood swings, vaginal dryness, and irritability. HRT can be prescribed to alleviate these symptoms. It can also provide protection from cardiovascular disease and osteoporosis, both of which can result from diminished hormone levels. In addition, estrogen has been studied for prevention against AD and its anti-aging benefits. A study published last year in the Journal of the American Medical Association estimated that for more than 99% of healthy perimenopausal women, the benefits of HRT outweigh the risks. PR 10/6/98

Eat to Beat AD - The Oxford Project to Investigate Memory and Ageing (Optima) says AD may be caused by a vitamin-deficient diet since the group has found a direct link between low levels of two vitamins - B12 and folic acid - and the onset of AD. Those who had below normal levels of vitamin B12 came from patients who were four times as likely to develop AD. Those with similarly low levels of folate - a form of folic acid - were three times as likely to develop the disease. People who have the highest quantities of the amino acid homocysteine in their blood stream are four-and-a-half times as likely to develop AD. Both B12 and folate are required to ensure that homocysteine doesn't build up in the bloodstream. BBC News 10/21/98 citing New Scientist 10/24/98 citing Archives of Neurology 55:1449

Vitamin E May Help Aging Memory - A high intake of vitamin E may help ward off memory problems associated with aging according to researchers at the Karl-Franzens University in Graz, Austria. Those with low blood levels of the antioxidant were more likely than those with high levels to score poorly on tests of cognition, a catch-all term for intellectual functioning,
Such tests are used to measure mental decline in AD and other types of dementia. These observations are compatible with the view that some dietary antioxidants may protect against cognitive impairment in older people. However, the study could not determine if the low blood levels of vitamin E were an actual cause or an effect of memory problems. Reuters 11/3/98 Journal of the American Geriatrics Society 1998;46:1407-1410 (Nov. 98)

Other Items
Partial View, An Alzheimer's Journal - Cary Henderson, a history professor, learned in 1985 he had AD. Frustrated by his failing memory and his physical inability to write, he began to use a tape recorder. Cary made countless hours of tapes, which his daughter, Jackie, his wife Ruth and Washington Post photographer Nancy Andrews edited. The tapes, transcripts and Andrews's photos are combined at http://www.washingtonpost.com/wp-srv/photo/partial_view/front.htm
to form the Web version of a new book: Partial View, An Alzheimer's Journal.

NBC Today Show Has 3 Part Series on AD - On Oct 5-7, 1998 the 3 parts were presented by Ann Curry. The video is on the internet. Go to the third show at http://www.msnbc.com/news/203012.asp   where there are the video links for the three shows at three speeds of 28.8, 56.6 and T1. The first "AD: Can It Be Diagnosed?" is 5 min 58 sec, the second is "Treating AD" at 6:18 and the third is "AD: Advice for Caregivers" at 6:18.

Leading Causes of Death - The National Center for Health Statistics discloses the leading causes of death in 1997 based on an annual review of death certificates. No. 1 is heart disease (725,790), No. 2 is cancer (537,390) and No. 3 is stroke (159,877). In 12^th place is AD (22,527). AP 10/7/98

President Clinton to Present 18 Finalists With Prestigious National Service Award at White House Ceremony on Friday Oct. 23, 1998 - The Foundation for Interfaith Research and Ministry (FIRM) Houston, Texas was cited as follows. "Working with 85 Jewish and Christian congregations, FIRM began by providing care teams that work with people with HIV/AIDS. It now works with families with members suffering from AD and other dementia diseases and with frail elderly. The AIDS Care Team program has been replicated in 30 states. Since 1992, the senior Care Teams have served 320 caregivers." PR 10/21/98

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