Alzheimer Related News Items

News as of 12 /5/04

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Top Items

A New Species of Amyloid Peptide - The report of this new species of amyloid peptide in Journal of Biological Chemistry was selected by the editors as the paper of the week. The editors described it is follows. One of the characteristic features of AD is the aggregation and eventual deposition of amyloid peptides in the brain. These amyloid deposits are generally composed of 39-43-amino acid residue amyloid {beta}-peptides that are derived from a large amyloid precursor protein through a series of cleavage events. Guojun Zhao and colleagues have now identified a new species of amyloid {beta}-peptide that is 46 amino acids long. The peptide is cleaved at a novel {zeta}-cleavage site, which is also the site of the APP717 or London mutation, a mutation often found in early-onset familial AD. The cleavage event leading to the new peptide is presenilin- dependent and is inhibited by {gamma}-secretase inhibitors that act as transition state analogues but interestingly is less affected by non-transition state {gamma}-secretase inhibitors. The discovery of a new 46-amino acid amyloid peptide is significant because the longer amyloid {beta}-peptides are more amyloidogenic and more pathogenic than the shorter ones. The identification of a new amyloid {beta} peptide species provides new insights into {beta}-amyloid precursor protein processing intermediates and could present a new target for treating AD. J. Biol. Chem. 2004, 279, 50647-50650 (Dec. 3 2004) and this editor note at 99926

Study Cites Risks in High Doses of Vitamin E - High doses of vitamin E, often viewed as a panacea for cancer, heart disease and other illnesses, actually increase the risk of death slightly among the elderly and infirm, researchers said 11/10/04. A study found that the increased risk of death was small, about 5% for those who had taken larger doses of the vitamin for at least five years. But vitamin E is taken by so many people — an estimated 25% of the American population — that even a small increase is significant, the researchers said. “People take vitamins because they believe it will benefit their health in the long term and prolong life,” said Dr. Edgar R. Miller III of the Johns Hopkins University School of Medicine, a coauthor of the study. “But our study shows that use of high-dose vitamin E supplements certainly did not prolong life, but was associated with a higher risk of death.” Miller presented the results 11/10/04 at a New Orleans meeting of the American Heart Assn., and they were simultaneously published online in the Archives of Internal Medicine. But some scientists were skeptical of the results. Dr. David Heber, director of the UCLA Center for Human Nutrition, noted that there was “a disconnect” between large studies like this one and smaller studies that had shown a benefit from taking vitamin E. Many of the people in the studies “were older people and had preexisting diseases. It’s hard to ascribe the bad outcomes to vitamin E, per se,” Heber said. The results came from a so-called meta-analysis that combined data on 135,967 patients in 19 separate studies. The combined results indicated an increased risk for patients – most of whom were over the age of 60 and suffering from heart disease or other illnesses – who took more than 400 international units, or IU, of vitamin E each day. The results said nothing about the effects of high doses in older people who were healthy or the effects in younger people. The study found no increased risk at doses below 200 IU, and possibly a slight benefit. By Thomas H. Maugh II and Valerie Reitman LA Times Staff Writers 11/11/04 Annals of Internal Medicine to be published in Jan 4, 2005, vol. 141, issue1. A free 11 page pdf Reprint is available at http://www.annals.org/cgi/reprint/0000605-200501040-00110v1.pdf

Drugs

Cholesterol Drugs May Not Reduce Risk of Dementia - New study findings suggest that the cholesterol-lowering drugs know as ‘statins’ do not appear to lower the risk of dementia or AD, except possibly in cases of early-onset AD. This runs counter to recent reports indicating that these drugs do, in fact, reduce the risk of dementia and AD. The authors of the current study believe the discrepancy may have to do with how the data were analyzed. Dr. Gail Li, from the University of Washington in Seattle, and colleagues assessed the outcomes of 2,356 elderly subjects without dementia who were in a health maintenance organization. The subjects were enrolled in the study between 1994 and 1996 and were evaluated every two years until the end of 2002. During follow-up, 312 subjects were diagnosed with all-cause dementia and 168 had probable AD. As noted, statin use did not have a significant effect on the risk of dementia or AD. Moreover, there was no evidence that higher or lower doses of statin affected the development of dementia. “Our results argue against the general premise that statins used for prevention of coronary heart disease will result in prevention of dementia or AD, except perhaps in subgroups at high risk for early-onset AD or in persons starting statins at a younger age and taking them for longer periods of time,” Li’s team concludes. Reuters Health 11/15/04 Neurology 2004;63:1624-1628

Drug May Ease AD-Related Memory Defects - Mice with a form of AD when treated with the drug rolipram appear to produce lasting improvement in learning and memory deficits, investigators at Columbia University report 12/1/04. Rolipram is being studied for treating a number of conditions ranging from depression to multiple sclerosis, even spinal cord injuries. The researchers theorize that it may stabilize synaptic circuits -- the connections between nerves. “This is the first demonstration that treatment with an agent known to directly affect the molecular machinery of memory can lead to long-lasting strengthening of the connection between nerve cells, and protect them from damage by beta-amyloid, the molecule responsible for cellular damage in AD,” Dr. Ottavio Arancio told Reuters Health. With his colleagues they saw that one 3-week course of rolipram injections improved abnormalities in synapses, learning, and memory in mice engineered to develop a form of AD. “Rolipram re-establishes normal memory” in these animals, Arancio said. “Significantly, this improvement persisted for at least two months after drug treatment was stopped.” It is noteworthy, he added, that rolipram’s beneficial effects are actually greater in older animals. “This work suggests that not only can treatment with rolipram ... counteract the toxic effects of high levels of amyloid protein in AD, but that it has the potential to delay the natural progression of the disease,” Arancio concluded. By Megan Rauscher Reuters Health 12/1/04 Journal of Clinical Investigation 114(11):1624-1634 (Dec. 2004) A copy in pdf form is free at http://www.jci.org/cgi/reprint/114/11/1624.pdf

ExonHit Therapeutics Accelerates Its Clinical Development Program in AD - ExonHit Therapeutics, a privately-held drug discovery company, announced 11/22/04 that it plans to start a Phase IIa proof-of-concept study in AD with EHT 0202, its most advanced compound in development, in the early part of 2005. ExonHit Therapeutics has already demonstrated that EHT 0202 improves attention and cognition and has neuroprotective properties in animal models. Based on these data it is likely that EHT 0202 may prove suitable for symptom relief and as a disease modifying agent in patients with AD. PR 11/22/04

Genes & Genetic Issues

Study Reveals Possible Location of AD Genes - Researchers at Columbia University Medical Center have found two locations in the human genome that may harbor genes which increase the risk of AD. If confirmed, they will be the first genes linked to the disease since ApoE4 was discovered in 1993. “We feel confident that we may be closing in on new AD genes,” says the study’s senior author, Richard Mayeux, co-director of the Taub Institute for Research on AD and the Aging Brain at CUMC. “This is a major collection of families, and family studies really give you more confidence that the region you’re looking at is significant.” Researchers think that AD is caused by the interaction of several different genes, but so far only one gene, ApoE4, has been linked conclusively to the disease. Finding the other genes will be a huge step toward understanding how AD begins and how it can be treated. It will also allow clinicians to predict who will develop AD later in life and who will benefit from drugs that prevent the disease. The new study found strong evidence for new AD genes on chromosomes 18 and 10. The region on 18 had never been strongly linked to the disease before, but the link to chromosome 10 confirms previous findings by other AD researchers. PR 11/1/04 Molecular Psychiatry Nov. 2004 vol 9, no. 11:1042-1051

2 Stem Cell Options Presented Human Embryos Wouldn’t Be Killed - The panel of experts that advises President Bush on bioethical issues heard descriptions 12/3/04 of two new laboratory techniques that may give scientists a way to get large numbers of medically promising stem cells without creating or killing human embryos. The two proposals were greeted enthusiastically, with several panel members saying the techniques, still in the experimental stage, may hold the promise of solving one of the most contentious bioethical dilemmas of the past decade. “If this pans out scientifically, it will be a major step forward. It may provide an opportunity to get through the political impasse,” said Leon R. Kass, the physician who chairs the President’s Council on Bioethics. In one technique, scientists would harvest viable cells from embryos created to treat infertility but which have stopped developing and are functionally dead. Taking the cells -- which can grow into stem cells -- would be analogous to removing organs of brain-dead accident victims for transplant. In the second technique, scientists would intentionally sabotage a cloning process called “nuclear transfer” so that the resulting bundle of cells is not an embryo but still has stem cell precursors. They could then be removed and used. The purported advantage of both techniques is that neither involves an embryo with the potential for growth. In the first, the embryo has already died; in the second, it never existed. By David Brown Washington Post Staff Writer 12/4/04

Long-term Memory Protein ‘Found’ - The identity of the protein which is key to developing long-term memory has been confirmed by scientists at the National Institute of Health. The discovery may lead to advancements in treatment for AD and other people with memory loss. Scientists have suspected for a long time that the mBDNF protein plays a role in memory development. But the NIH team claims to have proved the protein is the key, using experiments on mouse brains. The protein mBDNF, which stands for mature brain-derived neurotrophic factor, is produced by a chemical reaction involving the enzyme plasmin and proBDNF. The team carried out a series of experiments on mice brains, which are easy to mutate, to see how the protein affected long-term memory and what was needed to create the protein. In tests where the mouse brain was incapable of producing mBDNF, long-term memory formation was not possible. But when the conditions were right to produce mBDNF, the researchers found long-term memory development was possible. Dr Bai Lu said the findings had the potential to treat people with AD. “The fundamental problem is the part of the brain associated with memory is dying. If you can stop it from dying or improve the functions of memory you can help patients with AD.” BBC News 11/8/04 Science vol. 306, 5695, 487-491 Oct. 15, 2004

Of Mice, Men and In-Between - Biologists call hybrid animals chimeras (ki-MER-ahs), after the mythical Greek creature with a lion’s head, a goat’s body and a serpent’s tail. They are the products of experiments in which human stem cells were added to developing animal fetuses. Chimeras are allowing scientists to watch, for the first time, how nascent human cells and organs mature and interact -- not in the cold isolation of laboratory dishes but inside the bodies of living creatures. Some are already revealing deep secrets of human biology and pointing the way toward new medical treatments. Perhaps the most ambitious efforts to make use of chimeras come from Irving Weissman, director of Stanford University’s Institute of Cancer/Stem Cell Biology and Medicine. Weissman helped make the first mouse with a nearly complete human immune system -- an animal that has proved invaluable for tests of new drugs against the AIDS virus, which does not infect conventional mice. More recently his team injected human neural stem cells into mouse fetuses, creating mice whose brains are about 1 percent human. By dissecting the mice at various stages, the researchers were able to see how the added brain cells moved about as they multiplied and made connections with mouse cells. Already, he said, they have learned things they “never would have learned had there been a bioethical ban.” Now he wants to add human brain stem cells that have the defects that cause Parkinson’s disease, Lou Gehrig’s disease and other brain ailments -- and study how those cells make connections. Scientists suspect that these diseases, though they manifest themselves in adulthood, begin when something goes wrong early in development. If those errors can be found, researchers would have a much better chance of designing useful drugs, Weissman said. And those drugs could be tested in the chimeras in ways not possible in patients. Now Weissman says he is thinking about making chimeric mice whose brains are 100 percent human. He proposes keeping tabs on the mice as they develop. If the brains look as if they are taking on a distinctly human architecture -- a development that could hint at a glimmer of humanness -- they could be killed, he said. If they look as if they are organizing themselves in a mouse brain architecture, they could be used for research. So far this is just a “thought experiment,” Weissman said, but he asked the universitys ethics group for an opinion anyway. “Everyone said the mice would be useful,” he said. “But no one was sure if it should be done.” By Rick Weiss Washington Post Staff Writer 11/20/04

Caregivers

AD Steals More Than Memory - Though memory loss is the best-known AD symptom, the disease can also cause psychiatric problems that lead to profound changes in personality, mood and behavior. People who were happy and good-natured for most of their lives suddenly become fearful, depressed, deluded or angry, sometimes even violent. Many families hide such symptoms, and perhaps as a result, psychiatric problems were long thought to affect only a minority of people with AD or other types of dementia. Only recently has it become clear that emotional and behavioral troubles are nearly universal among people with AD, and the problems are frequently intractable and more upsetting to families than the mental slowing. Depression and apathy are the most common psychiatric symptoms. But agitated, aggressive and psychotic behaviors are a leading reason AD patients are put into nursing homes. (The other is incontinence.) “They are extraordinarily distressing and wearing on caregivers,” said Dr. Constantine Lyketsos, a psychiatrist and AD expert at Johns Hopkins. The emotional disorders can be difficult or impossible to treat. There is no drug specifically approved for psychiatric problems in patients, so doctors try to treat the symptoms, using drugs meant for other illnesses. They prescribe a wide array of medicines, including antidepressants, antipsychotics used to treat schizophrenia and stimulants and drugs approved for anxiety, epilepsy and memory impairment. Sometimes the drugs seem to work, sometimes they do not. Dr. Lon Schneider, a psychiatrist who studies and treats AD at the University of Southern California, said: “Whenever you see a long list of drugs of different classes, you know there’s no good treatment. You get a high degree of uncertainty, and companies hyping their antipsychotics.” Over all, Dr. Lyketsos said, the effects of the drugs are moderate. But he added that depression seemed to be the most treatable symptom, and could be eased in half to two-thirds of AD patients with drugs like Prozac, which enhance brain levels of the chemical serotonin. But some psychiatric drugs can have troubling side effects, particularly antipsychotics, which may increase the risk of stroke, diabetes, weight gain, high cholesterol, sleepiness and Parkinson’s-like movement disorders. Meanwhile, behavior therapy and activity programs at adult day care centers may work at least as well as drugs in some patients, and families are urged to try them first. Teaching relatives and the nursing home staff what to expect from a person with dementia and how to avoid confrontations can help to keep the peace. By Denise Grady NYTimes 11/2/04

Aggression Neurological - Caregivers of AD patients can now be reassured the aggressive behaviours seen in some patients are due to neurological changes in the patient’s brain – and not the patient being uncooperative. An imaging study using single photon emission computed tomography (SPECT) conducted in Toronto found aggressive AD patients were more likely to have decreased blood flow in the right middle medio-temporal lobe compared with those who were not aggressive. “The study confirmed that aggression was separate from cognitive decline,” said Dr. Krista Lanctôt (PhD), principal investigator of the study and a scientist in the neurosciences research program at Sunnybrook and Women’s College Health Sciences Centre. “People thought it was part of the cognitive decline and didn’t really know what was going on, but this proves that people with aggression have a different course of the illness than people who are not aggressive,” Dr. Lanctôt said. “It reassures the caregivers that it isn’t the patient just not trying. Sometimes the caregivers think that the person is being difficult or defiant, but there really is a difference. It is not the patient’s fault,” she added. By Kylie Taggart Medical Post vol. 40, issue 44, 11/23/04

Testing

Test Could Spot AD Early - A new nanotechnology-based technique could lead to a test for diagnosing the early signs of AD. The Bio-Barcode-Assay can recognise ADDL, a protein that accumulates in the brains of sufferers. It is a million times more sensitive than conventional tests and could revolutionise disease detection. In future, it might form the basis not only of a test for AD but also for types of cancer, the human form of mad cow disease and HIV. “Diagnosis [of AD] is 100% accurate post-mortem. What you want is the ability to detect the marker so you can begin to think about new types of therapies,” said Professor Chad Mirkin, of Northwestern University in Evanston, Illinois. Professor Mirkin and his research group at Northwestern developed the highly sensitive test by manipulating molecules at the nanometer scale (one billionth of a meter). “We have done the first set of experiments that quantify the number of ADDLs in cerebrospinal fluid,” Professor Mirkin said. ADDLs are protein bundles which attack nerve synapses in the brains of people with AD. “Nobody is able to study this with the existing tools. A nanotechnology-enabled tool is allowing us to study these kinds of markers and link them to disease. The next exciting step would be to move to blood. If you detect it in blood, you have a huge win.” By Paul Rincon BBC News science reporter 11/12/04

See other ADDL story as first one in Other Items

Iris Murdoch’s Last Novel Shows Signs of AD - Iris Murdoch, one of the greatest British novelists of the 20th century, revealed the first signs of AD in her final novel, researchers reported 12/1/04. Her manuscripts were handwritten with little editing, which allowed researchers to study the effects of early AD on writing. A comparative study of three of the award-winning writer’s works shows the vocabulary of her last novel “Jackson’s Dilemma,” is different from her earlier books and consistent with changes patients experience early in the illness. Murdoch was diagnosed with AD shortly after the book was published in 1995. She died in 1999. “Iris,” a film about Murdoch, starring Judi Dench and Kate Winslet as the novelist at separate stages in her life, came out in 2001. Using specialized software they transformed the texts into word lists and examined the variety of vocabulary and the rate at which she introduced new words. Although the grammatical structure remained the same, the vocabulary seemed to be enriched between the early and middle stages of her career and then declined in her final work. Dr Peter Garrard, of University College London, who headed the research team said the findings showed the smallest number of word types were found in the final novel. In the early stages of AD many patients have difficulty finding words, particularly for abstract terms. Reuters 12/1/04 Advanced Access published in the online journal Brain, doi:10:1093/brain/awh341 The story is reported orally at the NPR web site – a 5 min 50 sec report - click on Listen at http://www.npr.org/templates/story/story.php?storyId=4199817

Prevention

Obesity Bad for Brain, Study Finds - Obesity is harmful to the brain for women, but it doesn’t appear to raise the risk of dying for men who have suffered heart attacks, according to two new studies. Swedish researchers say that women who have been obese throughout their lives are more likely to lose brain tissue in the temporal lobe compared with women of normal weight. Loss of brain tissue has been linked to cognitive decline and an increased risk for AD. Obesity is a well-known risk factor for heart disease, but a separate study surprised researchers by finding that it didn’t increase the risk of death in men who had already suffered a heart attack. The Swedish paper “is the first study to show [that] a higher body mass index is related to brain atrophy,” said lead researcher Deborah Gustafson, a psychiatrist at Sahlgrenska University Hospital in Göteborg. The only significant relationship between body mass index (BMI) and brain atrophy was found in the temporal lobe, Gustafson said. “The temporal lobe is important for a number of reasons, including hearing, speech, language, comprehension, naming, memory, and visual processing of, for example, faces,” she said. By Steven Reinberg HealthDay Reporter 11/22/04 Neurology 2004;63:1876-1881

An Apple a Day Could Help Protect Against Brain-cell Damage, Cu Studies Find - A group of chemicals in apples could protect the brain from the type of damage that triggers such neurodegenerative diseases as AD and Parkinsonism, according to two new studies from Cornell food scientists. The studies show that the chemical quercetin, a so-called phytonutrient, appears to be largely responsible for protecting rat brain cells when assaulted by oxidative stress in laboratory tests. Phytonutrients, such as phenolic acids and flavanoids, protect the apple against bacteria, viruses and fungi and provide the fruit’s antioxidant and anti-cancer benefits. Quercetin is a major flavanoid in apples. Antioxidants help prevent cancer by mopping up cell-damaging free radicals and inhibiting the production of reactive substances that could damage normal cells. “The studies show that additional apple consumption not only may help reduce the risk of cancer, as previous studies have shown, but also that an apple a day may supply major bioactive compounds, which may play an important role in reducing the risk of neurodegenerative disorders,” says Chang Y. “Cy” Lee, professor of food science at the university’s New York State Agricultural Experiment Station in Geneva. “What we found was that the apple phenolics, which are naturally occurring antioxidants found in fresh apples, can protect nerve cells from neurotoxicity induced by oxidative stress,” Lee said. By Susan S. Lang PR 12/2/04 Journal of Food Science Nov./Dec. 2004 69(9):S357-60

A Workout for Your Brain - You can keep the mind fit through mental and physical activity.

At UCLA seniors took part in a class aimed at enhancing their cognitive abilities. Dr. Gary Small, director of the UCLA Center on Aging launched the memory training classes on campus. He is the author of “The Memory Prescription.” Through a series of “mental aerobics” activities, the class participants learned memory strategies and exercises to help keep their minds in shape. In addition to such brain-training classes that are now offered in some cities, various books, videos and web sites are devoted to helping people boost their memory. And early next year, chapters of the Alzheimer’s Association are planning to offer “Maintain Your Brain” workshops to educate people about lifestyle measures -- including mental and physical activity -- to help preserve their cognition. Research has demonstrated, for example, that higher levels of education and plenty of mental stimulation throughout life are associated with lower rates of AD, he notes. A study published last year in The New England Journal of Medicine found that people over 75 who often read, danced and played board games or musical instruments had lower rates of dementia, including AD, than those who didn’t frequently engage in such stimulating pursuits. “It’s the use-it-or-lose-it theory,” Small says. “If you keep your brain cells active it improves their efficiency. You develop what we believe is a cognitive reserve” and it’s never too late to start. Even people who are at high risk of AD because of a family history of the disease may see benefit. They may not completely steer clear of the disease, but they may reduce or delay its symptoms for months or even years, according to Small and others. Dr. Bill Thies of the Alzheimer’s Association says staying mentally active -- be it through working crossword puzzles, reading, taking college courses, learning a new language, playing games or going to the theater -- is “the prudent thing to do” as we age. “But it doesn’t come with a guarantee card, unfortunately.” The same goes for physical activity, according to Thies. Researchers know that people who exercise regularly have healthier brains and less AD than their couch-potato counterparts, though they don’t know exactly how much or what specific kinds of exercise offer the most protection. Research published in September in the Journal of the American Medical Association found that even walking appears to have a significant benefit. By Jacqueline Stenson Contributing editor MSNBC (www.msnbc.msn.com) 11/30/04

Work Demands May Influence Dementia Risk - Highly challenging jobs with opportunities for responsibility may be good for your resume and your health. New study findings suggest that people with these types of jobs may be less likely to be diagnosed with AD or other types of dementia. “Challenging work with high control possibilities and high social demands might prevent the development of dementia,” study author Dr. Andreas Seidler, of Johann Wolfgang Goethe University in Frankfurt, Germany told Reuters Health. Other psychosocial factors have also been linked with an increased risk of dementia among adults, according to the report. Previous researchers have found that adults who live alone, have never married, have no close social ties, or who rarely participate in social and leisure activities have an increased risk of dementia. Seidler and colleagues looked at the possible influence of work-related factors on dementia risk. They studied the work histories of 195 dementia patients, age 55 to 99 years, who visited 23 general practices between 1998 and 2000. For comparison, the study also included 229 seniors without dementia. Dementia patients were less likely to have had challenging work experiences or high possibilities for control at their jobs than those in the comparison group, Seidler and colleagues report. By Charnicia E. Huggins Reuters Health 11/26/04 Occupational and Environmental Medicine, December 2004

Other Items

Findings Show How Toxic Proteins Rob AD Patients of Memory - Researchers at Northwestern University have discovered a molecular mechanism -- a tiny protein attacking nerve cells -- that could explain why the brain damage in early AD results in memory loss and not other symptoms such as loss of balance or tremors. The research team, led by William L. Klein, professor of neurobiology and physiology, found that toxic proteins, called “amyloid ß-derived diffusible ligands” (ADDLs, pronounced “addles”), from the brain tissue of individuals with AD specifically attack and disrupt synapses, the nerve cell sites responsible for information processing and memory formation. These results show that only particular neurons and synapses are targeted by the neurotoxins. An understanding of how ADDLs disrupt synapses without killing neurons could lead to the development of new therapeutic drugs capable of reversing memory loss in patients who are treated early, in addition to preventing or delaying the disease. “Memory starts at synapses, so it was probable that AD would be a synapse failure,” said Klein. “Our work, which shows that ADDLs bind with great specificity to synapses, is the first demonstration of that.” PR 12/1/04 The Journal of Neuroscience Nov. 2004;24:10191-10200 See other ADDL story in Testing

Diabetes in Midlife Linked to Later Dementia - Middle-aged people with diabetes are nearly three times more likely to develop dementia in old age than people without diabetes, according to a new study. Studies looking at a cross-section of the population have “tied diabetes to AD or dementia,” Dr. Michal Schnaider Beeri, from Mount Sinai School of Medicine in New York, told Reuters Health. “Our study is special because it shows a strong association between these disorders over several decades.” The study involved 2600 subjects who participated in an Ischemic Heart Disease study in the 1960s and were still alive and available for follow-up in 1999. The subjects were between 40 and 65 years of age when the study began. The mental status of 1892 participants was determined, and 652 were identified as possibly demented. This was confirmed in 309 subjects (16.3 percent). Those with diabetes during the study were 2.83 times more likely to develop dementia than those without diabetes, the investigators report. By Anthony J. Brown, MD Reuters Health 12/1/04 Neurology 2004;63:1902-1907

Computer Simulation Shows How Fibrils Form - To get a better look at how proteins gather into clusters called amyloid fibrils - which are associated with important human diseases such as AD, Parkinson’s and the so-called prion diseases like Mad Cow - researchers at North Carolina State University decided to make movies. Dr. Carol Hall, Professor of chemical engineering at NC State and Hung D. Nguyen, a graduate student in Hall’s lab, used a computer simulation technique, discontinuous molecular dynamics, to visualize the meanderings of small proteins called peptides. Movies of the simulation show that 96 randomly placed peptides spontaneously aggregate into what Hall calls a “sandwich” of layered protein sheets, similar to the amyloid fibrils discovered in diseased people and animals. Hall says that understanding how fibrils form in human or animal organs may lead to discoveries of how to slow or halt fibril formation. PR 11/22/04 Proceedings of the National Academy of Sciences Nov. 16, 2004 vol. 101, no.46:16180-16185

Elan Corporation and Mayo Announce Settlement of Patent Suit Involving AD Research - Elan Corporation, plc and Mayo Foundation for Medical Education and Research (Mayo) jointly announced 11/12/04 that they have entered into an agreement related to each party’s AD research efforts. The agreement resolves a patent dispute regarding certain transgenic mice patents and facilitates use by both parties of an array of research tools in combating the disease. The Elan patents that were the subject of the dispute - which are acknowledged as valid and enforceable under the agreement - cover transgenic mice that express the human gene known as the Swedish mutation of the amyloid precurser protein. These mice serve an important function in the study of AD and the development of drugs aimed at curing the disease. The resolution of this dispute provides Mayo and Elan with cross-licenses necessary to pursue their respective ongoing AD research and development efforts, and includes the ability for Mayo to conduct research with third parties under this portfolio. Both entities remain committed to changing the course of AD through these efforts and by making their patents available for licensing. PR 11/12/04

Boston Biomedical Research Institute and Wyeth Announce Licensing of AD Immunother- apy Technology - Boston Biomedical Research Institute (BBRI) has announced that it has entered into an agreement with Wyeth Pharmaceuticals to license BBRI’s patented technology for immunotherapy to combat AD. This agreement will further the Elan and Wyeth collaboration with BBRI on beta amyloid immunotherapy for the treatment of AD. The ground-breaking work forming the basis for the patent applications was conducted in the lab of Dr. Vic Raso, a senior scientist at BBRI. PR 11/22/04 To see three of Raso’s published patent applications go to http://www.uspto.gov/patft/index.html and in the Published Applications side on the right click on “Advanced Search” and in the Query window type “IN/Raso” (without the quotes) and then click on the Search button

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