Alzheimer Related News Items

News as of 6/05/00
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Genes & Genetic Issues
Alzheimer Brain Damage Differs Between Sexes - Imaging studies of the brains of AD patients suggest that damage to the brain's white matter is more common and more severe in women than men, Japanese researchers at Kyoto University report. Moreover, they found a gene called apoE4 was not associated with the presence or the degree of cerebral white matter (damage) in AD, as had been theorized. AD is a debilitating disorder that features a distinct kind of damage to the white matter of the brain. They looked at whether these white matter injuries could be linked in some way to the apoE4 variant, since the gene has also been implicated in similar kinds of brain damage. The team also examined whether factors such as sex, age... hypertension, (or) diabetes mellitus" might play a role in mediating the white matter damage. The study subjects included 55 patients with the disease and 66 healthy subjects. They found that over 65% of the AD patients had the tell-tale white matter damage. But, they were unable to demonstrate a statistically significant relation between the E4 (gene variant) frequency and the lesion grades. However, a significant risk factor for the presence of white matter (damage) is sex since the white matter lesions were more common in female patients. Although there is no sure explanation for this sex difference, they theorize that the estrogen decline in menopausal women may be related to the degenerative damage in the cerebral white matter. They call for more research to explore this apparent white matter damage difference between the sexes. Reuters Health 5/10/00 Journal of Neurology, Neurosurgery and Psychiatry 2000;68:653-

Genetic Researchers Announce Big Step in Sequencing Smallest Chromosome - Researchers in Japan and Germany announced 5/8/00 a breakthrough in the human genome project -- Chromosome 21, the smallest chromosome in the human genome, has become only the second human chromosome to be fully sequenced. The genetic information on Chromosome 21 has been linked to Down Syndrome, one form of AD, and several types of cancer including Lou Gehrig's disease. Chromosome 21 contains only 225 active genes. CNN 5/8/00

Stem Cells Repair Spinal Damage in Rats - Stem cells from embryos -- cells that can give rise to various specialized types of cells -- could help repair damage to the fatty sheaths that surround nerve cells, according to results of a new animal study. The technique holds promise for the treatment of spinal cord injuries and diseases such as multiple sclerosis and AD, researchers report. Earlier research had shown that stem cells taken from rat embryos can be coaxed into forming nerve cells called oligodendrocytes. These cells are essential for the formation of myelin, the fatty material which lines the body's network of axons. The researchers at the Washington University School of Medicine in St. Louis, Missouri, took embryonic stem cells and transformed them into oligodendrocytes. Laboratory testing showed that these cells were able to form myelin within a little over a week, the researchers report. In earlier experiments, mature nerve cells taken from rat brains or spinal cords had taken 4 to 6 weeks to form the myelin. Dr. John W. McDonald told Reuters Health in an interview that "This is paving the way to demonstrate the usefulness and safety of this type of cells so they can be used in humans,'' Although federal regulations prohibit the use of federal funds for research involving human embryonic cells, McDonald said he expects that this ban will be lifted eventually. Hopefully, stem cells will be used to repair human myelin within the next 5 years, he said. Reuters Health 5/22/00 Proceedings of the National Academy of Sciences 2000;97:6126-

DNA Arrays Promise Personalized Medicine - Researchers are on the verge of developing a DNA analysis machine so powerful that it can monitor the activity of individual cells. Coupled with the flood of information expected from the Human Genome Project, DNA arrays could revolutionize science and medicine. Researchers predict more accurate and earlier diagnosis, better drugs, even the discovery of previously unknown diseases. In terms of drug development LifeSpan BioSciences, a small biotechnology company based in Seattle, hopes to figure out which genes are turned on in particular diseases -- and to sell that information to pharmaceut ical companies. Drug companies come to LifeSpan with genes that they believe might be useful targets for drugs. LifeSpan uses customized DNA arrays to identify where and when those genes are turned on in both healthy and diseased cells. If a drug company had a collection of genes that are active in people with AD, for example, LifeSpan could search for the one that is turned on in the brain during the earliest stages of the disease. Whatever protein that gene made might be the best target for a new AD drug. "The ultimate goal of this technology is to localize every gene in the human body, and every gene in all major diseases" says chief scientific officer Glenna Burmer. As that information comes out, LifeSpan scientists predict a wave of new treatments for diseases such as AD, cancer and arthritis that until now have been very hard to attack. AP 5/29/00

Gene Responsible for Aging Found in Yeast - Researchers have discovered that the secret to slowing the aging process in yeast is calorie restriction and have also identified the gene involved, a finding that could have potential for the development of anti-aging therapies. They report their research 5/24/00 at the 100th General Meeting of the American Society for Microbiology. Caloric restriction, which is the reduction of caloric intake without malnutrition, is a time proven method for extending the life span of mammals and postponing the manifestations of aging, including both functional decline and age-related diseases. Dr. Michal Jazwinski of the Louisiana State University has developed the yeast Saccharomyces cerevisiae as an experimental model for the molecular analysis of the aging process. He discovered that manipulating the nutritional intake of yeast cells can increase their life spans, providing a useful model for the molecular analysis of caloric restriction. Not only has Dr. Jazwinski shown that caloric restriction extends the life span of these cells but it also postpones many of the physical manifestations of aging. In a related study, Dr. Leonard Guarente of the Massachusetts Institute of Technology announced that his lab has identified a gene, SIR2, which regulates the life span of yeast. The gene is responsible for the production of a protein, Sir2, and the higher the level of this protein, the longer the life span of yeast cells. Sir2 is responsible for a process called genomic silencing that Dr. Guarente believes helps slow the aging process. "Our findings thus provide a model for aging that is universal and explains how calorie restriction extends life span," says Dr. Guarente. "We believe that these studies could lead to the development of a drug that intervenes to strengthen the Sir2-silencing process and provides the benefits of calorie restriction without the extreme difficulty of the regimen itself." PR 5/24/00

SignalGene and National Research Council of Canada Enter Into Functional Genomics Collaboration on Neurodegenerative Disorders - The objective of the collaboration is to identify novel targets for the development of new therapeutic drugs for the treatment of central nervous system disorders, such as AD and Parkinson's diseases. SignalGene scientists will apply the Company's proprietary technologies to analyze gene expression patterns in human pathology samples and biological models of neurodegeneration prepared for or developed by NRC researchers. The core technology, termed STAR (for Subtractive Transcription-based Amplification of mRNA), is a novel, patented process for identifying gene transcripts that are increased or decreased in cells. Dr. Michael Dennis, President & CEO of SignalGene, commented that this collaborative program complements their ongoing genetics-based program for late-onset AD being pursued in partnership with Genset S.A. PR 5/25/00

Imaging Technique Reveals Details on AD Damage - A novel imaging technique is providing important clues to the brain damage present in patients with AD and other forms of dementia. Brain structures called microcolumns, consisting of nerve cells linked together vertically, are disrupted in the brains of AD patients. These changes have been visualized using a sophisticated imaging technology based on statistical physics to visualize and analyze brain tissue. They examined the anatomical organization of the brain's cortex. The cortex is the outer layer of grey matter that covers most of the brain's hemispheres. It governs and integrates key brain functions including thinking, behavior, perceptions and general movement. The team found that in AD brains, there appeared to be "a loss of over 95% of the area normally occupied by this unique architectural microcolumn component of the cortex." These structures "may hold the key to understanding, and perhaps reversing, the ravages of this devastating disease," Dr. H. Eugene Stanley noted in a statement. The study is the first to compare microcolumns in diseased brains to those in healthy brains. It appears that the disruption present in these dementing diseases correlates with the degree of dementia. In an accompanying commentary, Dr. Edward G. Jones at the Center for Neuroscience at the University of California, Davis, reviewed some of the history of microcolumnar research and observed that many questions remain to be answered. Jones concludes that "the jury is still out on whether anatomical microcolumns are fundamental units of organization in all cortical areas of all species" and suggests that "more comprehensive data on the intricacies of intracortical connectivity" is needed to settle these questions definitively. Reuters Health 5/19/00 Proceedings of the National Academy of Sciences 2000;97:5019-

Prevention
Smoking May Affect Mental Function - Smokers may be more likely than nonsmokers to experience a decline in mental function as they get older, according to a new report by Dr. Jorge A. Cervilla, of the Complejo Hospitalario San Luis, in Palencia, Spain. Cervilla and colleagues from the University of London, UK, report on the results of a study of 654 people aged 65 and older living in an inner-city neighborhood in London. Based on interviews conducted with the residents, the researchers calculate that elderly people who smoke are 3.6 to 4 times more likely to become mentally impaired than people who have never smoked. In determining the increased risk, the investigators took into account several factors that might have influenced the results, including depression, education and alcohol use. But when the researchers looked at alcohol use among the participants, they did not find any relationship between drinking and mental decline. Reuters Health 5/10/00 Journal of Neurology, Neurosurgery and Psychiatry 2000;68:622-

UK Scientists Urge Caution on Mobile Phone Use - British scientists on 5/11/00 warned parents to curb children's use of mobile phones and called on the British government to toughen up rules for phone transmitter masts as a precaution against potential health risks. They concluded that it is not possible at present to say that exposure to radiation, even at levels below national guidelines, is totally without potential adverse health effects, and that the gaps in knowledge are sufficient to justify a precautionary approach. The scientists recommended discouraging regular use of mobiles by children, suggesting those under 16, and said the industry should not market to that age group. A source close to the inquiry told Reuters that the scientists were worried by "odd findings." "One odd finding came up when we looked at microwave radiation on nematode worms. That showed odd changes to the protein structure," said the source. "It was a kind of heat shock on the protein. You know, slightly cooked." The inquiry committee was established after a number of worldwide reports of radiation from mobile phones causing cancer, memory loss and AD. By Edna Fernandes Reuters 5/11/00

Cold Sore Virus Mimics AD Protein - Adding weight to the theory that viral infection may be involved in the onset of AD, researchers have found a possible link between the brain disease and herpes simplex virus. A team from the University of California at Irvine has found evidence that a snippet of protein found in the herpes simplex virus 1 (HSV1) -- a virus that causes cold sores -- mimics beta-amyloid, a protein that accumulates and forms the "plaques" found in the AD brain. The finding suggests that HSV1 infection, in addition to other genetic and environmental factors, may contribute to the development of AD. More study is needed to determine if the viral protein can affect the brain, which is a much more complex environment than a laboratory dish containing brain cells. However, the findings do bolster earlier work suggesting that if a virus helps cause AD, it may be herpes simplex. If indeed HSV1 can contribute to AD, then scientists may be able to develop a vaccine to prevent the disease. By Amy Norton Reuthers Health 5/12/00 Biochemistry May 16, 2000

Enzyme May Protect Nerve Cells Against Decreased Function and Premature Death - Telomerase, an enzyme believed to have a role in determining the life span of cells, also may protect nerve cells against decreased function and premature death caused by AD and other age-related neurological disorders, according to Mark Mattson, Ph.D., chief of the Laboratory of Neurosciences at the National Institute on Aging Gerontology Research Center in Baltimore. In experiments designed to mimic conditions in neurologically impaired brains, Mattson and his colleagues found that nerve cells with low levels of telomerase were particularly vulnerable to being killed by amyloid peptide, a toxic protein that accumulates in the brains of people with AD. In contrast, nerve cells with high levels of telomerase displayed a remarkable resistance to being damaged or killed in experimental models of AD or stroke. The researchers have found that telomerase blocks a biochemical cascade of reactions called apoptosis, which causes nerve cells to self-destruct. Accumulating evidence implicates the process of apoptosis in the death of nerve cells that occurs in AD, Parkinson's disease and stroke. If scientists can develop methods to stimulate the production of telomerase in nerve cells, Dr. Mattson said, it might help fend off age-related neurological disorders. PR 5/31/00 Journal of Molecular Neuroscience 6/2/00.

Scientists Link Alcohol Tolerance With AD - People who lack special enzymes needed to break down alcohol in their bodies have a greater chance of developing AD, according to Japanese scientists at the Nippon Medical School in Tokyo. In a study of about 900 people, half of whom had AD, the results showed that people without the special enzymes to break down alcohol were 2.5 times more likely to get the disease. About 40 percent of Japanese are said to lack such enzymes, resulting in a low tolerance for alcohol. Reuters 5/24/00

Aegera Therapeutics Inc. Formed - a New Canadian Biotechnology Company - Apoptogen and Exogen Neurosciences announced 6/1/00 they have merged to form Aegera Therapeutics Inc., building an integrated world class biotechnology company focusing on the treatment of neurological diseases and cancer. The merged company has a primary therapeutic focus in developing products to preserve the life of brain cells through signal transduction, and to control inappropriate and damaging cell death (apoptosis), which can lead to neurodegenerative diseases such as Parkinson's Disease and AD. PR 6/1/00

Reagan Kin Makes AD Appeal - Maureen Reagan promised on 5/30/00 to help find a cure for the illness that plagues her father and urged health care workers to educate doctors and families about the diagnosis and treatment of AD. Early diagnosis is key to helping patients, who now can sustain their cognitive health for several years thanks to drugs that didn't exist six years ago when her father was diagnosed, said Reagan, former President Ronald Reagan's oldest daughter. "Our goal is a world without AD,'' she said. "If we can get everybody energized about this ... if we can teach people to look for that click of awareness (of symptoms of the disease), we can find this disease early. She had previously spoken 5/16/00 to the California state lawmakers to spend $2.4 million on an AD education effort to help doctors and families recognize the early signs of the disease. Gov. Gray Davis had just proposed spending $2.4 million for a statewide AD disease education program in his state budget. Reagan wants lawmakers to endorse that plan. By Micelle DeArmond AP 5/30/00 and AP 5/16/00

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