Alzheimer Related News Items
News as of 10/09/05
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Researchers Claim 95 Percent Success in Predicting AD - A new study by a group at NYU School of Medicine says the earliest manifestations of AD can be found with a relatively inexpensive, painless, and easy-to-use tool called an EEG (electroencephalograph). The researchers claim a 95 percent success rate. The researchers found that a computer analysis of the EEG, which measures the brain’s electrical activity, accurately predicted healthy people in their 60s and 70s who would develop dementia over the next 7 to 10 years. It also identified individuals who would remain virtually unchanged over the same time span. The EEGs were almost 95 percent accurate in identifying those who would decline cognitively and those who would not, according to the study. “Our results suggest that quantitative analysis of the EEG is sensitive to the earliest signs of the dementing process,” says Leslie S. Prichep, Ph.D., Associate Director of the Brain Research Laboratories of the Department of Psychiatry, who led the study. Some day she says it may be used as one of the tools to evaluate a person’s propensity for developing AD, the most common form of dementia affecting people over 65. But for now the results need to be replicated in and validated by much larger prospective studies before they can be applied to screen large populations. It takes about 30 minutes to perform an EEG, which involves placing recording electrodes on the scalp. The test is perfomed with the patient seated comfortably. There are no injections and the scalp is not shaved. A prominent feature associated with cognitive deterioration on the baseline EEG was a brain wave called theta, which was excessive in people who would eventually decline, according to the study. This band was particularly abnormal in the frontal regions, along the lateral regions and in the right posterior region of the brain in those people who went on to decline. Another feature was a slowing in the mean frequency of the EEG, which is described in cycles per second. Yet another distinctive feature of those who decline was a change in the synchronization between the two sides of the brain. The source of the theta has been shown to be the hippocampus, a brain region demonstrated in imaging studies with MRI and PET to be impaired in dementia, notes Dr. Prichep. Seniors.com 10/6/05 To be published in the upcoming on-line issue of the journal Neurobiology of Aging
Drugs
Eisai Shares Jump after New AD Drug Report - A local Toyoko newspaper reported on 9/22/05 that the drug maker Eisai Co. Ltd. developed a compound that could become a new type of drug to treat AD. The compound, code-named E2012, had been disclosed by Eisai, Japan’s fourth-largest drug maker, as part of its pre-clinical development lists, but big play on the front page of the Nikkei Business Daily apparently caught investors’interest. The paper said that unlike current drugs that only lessen symptoms, the new compound may actually lead to a cure. Eisai shares were up to an all time high. For Eisai, mitigating the impact of the U.S. patent expiry of its key products is its biggest challenge. Its top-selling Aricept AD drug will lose its U.S. patent in November 2010. The paper said the compound inhibits the activity of an enzyme called gamma-secretase, which catalyses the cleavage of amyloid precursor protein to create beta-amyloid. Beta-amyloid is the protein that collects around cells in the brain and is though to be a cause of the symptoms of AD. Animal tests using mice have shown that E2012 prevents the accumulation of beta-amyloid in the brain, the paper said. Eisai said it planned to start clinical trials in the United Sates in the business year starting next April. Reuters 9/22/05
Medivation Announces First Patient Dosed in Phase II Trial with Dimebon for Treating AD - Medivation, Inc. announced 9/9/05 that patient dosing in its Phase II AD study with Dimebon began on September 8, 2005. This randomized, double-blinded, placebo-controlled study is being conducted at approximately 12 sites in Russia, and will enroll up to 166 patients. The study’s clinical endpoints are the same ones used by the U.S. Food and Drug Administration to approve all of the presently marketed AD drugs. Medivation estimates that patient dosing in this study will be completed by June 30, 2006. Dimebon has been approved for use in Russia as an anti-histamine since 1983. More recently, Dimebon was shown to bind to both of the two presently validated targets for the treatment of AD - cholinesterase and the NMDA receptor. In addition, Dimebon also blocks a third target which, while not yet validated for the treatment of AD, has been linked to AD in published literature. Dimebon has been shown to improve learning and memory in animal models of AD and in an open-label 14-patient pilot clinical study in AD patients. Genetic Engineering News 9/9/05
Poor Results for Axonyx AD Drug - Axonyx’s developmental drug Phenserine has produced disappointing results in phase III clinical trials for mild to moderate AD. Enrollment in the trials was halted after the drug’s lack of efficacy became apparent. Results following 12 weeks of treatment confirmed findings from a previous study in not showing a statistically significant benefit of Phenserine treatment over placebo. Patient recruitment for these studies had been halted and the planned 26 week treatment period shortened to 12 weeks based on the previously released results of a 375-patient trial. The company continues to evaluate the whole Phenserine program. There is an ongoing examination of the interim results from its ongoing phase IIb trial. The phase IIb trial seeks to evaluate the potential ability of Phenserine to lower the levels of beta-amyloid precursor protein in AD patients following six months of treatment. The reduction of the protein may lead to a slowing of disease progression. Pharmaceutical Business Review Online 9/22/05
Lancet Article Features Potential Use of Statins to Treat AD - The potential use of statins to treat AD is featured in The Lancet Neurology (Sept. 2005;4: 521-2). The article concludes that statins, which are used to lower cholesterol levels, may be useful in the prevention or delaying onset of AD, in treating the symptoms of AD, and in slowing disease progression. The article’s authors were M. Kivipelto, A. Solomon, and B. Winblad from the Karolinska University Hospital in Stockholm, Sweden. According to the article, “Delaying of the disease process would be of great clinical and public-health importance. Statins may be useful both in the prevention or delaying of onset, in treating the symptoms, and in slowing the progression.” Further trials are needed before statins can be officially recommended for AD treatment, and such trials are currently ongoing. Business Wire 9/12/ 05 Lancet Neurology Sept. 2005;4: 521-2
Genes & Genetic Issues
Researchers Announce Inflammation Breakthrough - Researchers in Texas, Wisconsin, and Australia announced 10/10/05 they have isolated the human gene that causes and controls inflammation, leading the way for inflammation control drugs which could treat conditions ranging from cancer to obesity. “Basically, what we’ve found is the gene that mediates inflammation, controls inflammation,” said John Blangero, Ph.D., a senior researcher at the private San Antonio research firm Southwest Foundation of Biomedical Research, and the lead researcher for the paper, which was published 10/9/05 in the journal Nature Genetics. Inflammation has been targeted as a contributing factor in heart disease, cancer, diabetes, AD, stroke, and obesity, mainly because the gene, labeled SEPS-1, triggers arterial wall hardening. “This discovery has definitely opened up an important area of information about a biological pathway that is critical to disease,” Blangero said in an interview 10/9/05. Blangero says inflammation as it exists in humans is useful in eliminating faulty proteins which are created by the stress of virulent diseases like typhoid fever. But he says in “western societies,” where those diseases have been controlled, inflammation serves a more negative role in our bodies, and this may be partially responsible for an upsurge in diabetes, AD, and obesity in recent decades. “I call it the garbage truck of the cell, that removes some of the unfortunate accidents of the cellular machinery,” Blangero said. Researchers began their quest for the inflammation gene by studying the desert sand rat which has a similar propensity for obesity and diabetes. Blangero’s team was brought in to determine whether the gene which was found to control those conditions in rates is similar in humans, and he says researcher with northern European and Hispanic populations has confirmed the role of SEPS-1 in controlling inflammation in humans. “We replicated out findings in another study with a different population of a different ethnic group,” Blangero said. “This is rare in human genetics, and adds to other clear evidence that SEPS-1 is a good target in defeating inflammation, which plays an important role in virtually every disease of major public health importance.” By Jim Forsyth WOAI San Antonia News 10/10/05 Nature Genetics published online Oct. 9, 2005 doi: 10.1038/ng1655
Study: Stem Cells May Repair Cord Damage - Injections of human stem cells seem to directly repair some of the damage caused by spinal cord injury, according to research that helped partially paralyzed mice walk again. The experiment, reported 9/19/05, isn’t the first to show that stem cells offer tantalizing hope for spinal cord injury - other scientists have helped mice recover, too. But the new work went an extra step, suggesting the connections that the stem cells form to help bridge the damaged spinal cord are key to recovery. Surprisingly, they didn’t just form new nerve cells. They also formed cells that create the biological insulation that nerve fibers need to communicate. A number of neurological diseases, such as multiple sclerosis, involve loss of that insulation, called myelin. “The actual cells that we transplanted, the human cells, are the ones that are making myelin,” explained lead researcher Aileen Anderson of the University of California, Irvine. “We’re extremely excited about these cells.” By Lauran Neergaard AP Medical Writer 9/19/05 Proceedings of the National Academy of Sciences, 102(39) 14069-14074
National Institute on Aging Awards $10 Million to Study Families with AD History - More than 500 families affected by AD are participating in a landmark study led by Columbia University Medical Center to find a genetic link to the disease. That number will now double to 1,000 under a new $10 million five-year grant from National Institute on Aging. The researchers hope to find a way to predict who will get AD. The new grant is a continuation of the National Institute on Aging Late-Onset AD (NIA-LOAD) study, led by a Genetics Coordinating Core (GCC) at Columbia University. The study has already overseen the collection of 2600 samples from 519 families, and the new grant will include follow-up and genotyping for these families. “Many steps in the development of the disease remain unknown, and we may be able to understand the process more fully with the discovery of more genes,” says the principal investigator Richard Mayeux, M.D., co-director of the Taub Institute for Research on AD and the Aging Brain. “We intend to identify the genes underlying AD with the hope that that this will help in the development of drugs to treat or possible prevent the disease altogether.” The researchers are interested in a protein called amyloid, which is known to be a factor in the disease. In AD amyloid somehow becomes misfolded and becomes toxic to nerve cells, likely setting up a cascade of inflammation. The researchers believe that teasing out the genes that regulate amyloid production and processing could be a major advance in understanding this disease. Although amyloid protein is known to be connected with AD, genes in other pathways may also be important. Medical News Today 10/1/05
Chromosome Transplant in Mice Could Provide Clue to Down’s Syndrome Illnesses - Scientists at the National Institute for Medical Research in London have successfully transplanted human chromosomes into mice, a first that promises to transform medical research into the genetic causes of disease. The mice were genetically engineered to carry a copy of human chromosome 21, a string of about 250 genes. About one in a thousand people are born with an extra copy of the chromosome, a genetic hiccup that causes Down’s syndrome. Genetic studies of the mice will help scientists to nail down which genes give rise to medical conditions which are prevalent among people with Down’s syndrome, such as impaired brain development, heart defects, behavioral abnormalities, AD and leukemia. By Ian Sample, Science Correspondent Guardian UK 9/23/05
Testing
PET Scans Predict AD in Cognitively Impaired Patients - Positron emission tomography (PET) imaging of glucose metabolism in the brain can accurately predict which patients with mild cognitive impairment (MCI) will progress to full-blown AD, researchers say. PET proved more accurate than screening for genetic predisposition to AD, Alexander Drzezga, M.D., of the Technical University of Munich, and colleagues reported in the October issue of the Journal of Nuclear Medicine. However, a combination of PET and genetic screening appeared to have the highest positive predictive value. PET imaging of the brain’s glucose metabolism using the radiotracer fluorodeoxyglucose (FDG) measures synaptic activity and can identify neurodegenerative processes in the brain, according to the German team. In the study, PET data were analyzed with an automated computer program that performed an observer-independent statistical comparison with an age-matched reference database. This approach has proved more accurate than observer-dependent approaches, the investigators said. All patients underwent neuropsychological evaluation, a PET imaging scan, and genetic screening for the APOE-e4 allele, which has been identified as a major susceptibility gene. About 16 months later, patients underwent a second neuropsychological evaluation to determine who had progressed to AD. PET scans suggested a likelihood of AD in 13 patients, and 11 of these progressed to dementia by the end of the study. Of the 17 patients with no suggestive PET findings, only one progressed to dementia. This test had a sensitivity of 92% (95% confidence interval=62-99), a specificity of 89% (95% CI=65-98), and a test accuracy of 90%. The positive predictive value was 85%. Genetic tests identified susceptibility in 17 of the patients, and nine progressed to clinical dementia by the end of the study. The positive predictive value was 53%. Combining both tests may be especially useful for identifying subgroups of patients with especially high or especially low risk, the investigators said. “The current study underlines that a genetic disposition does not necessarily represent a determined prognosis, thus, the need for measures that allow the definition of the actual onset of a disease process is apparent” Dr. Drzezga said. “Molecular imaging could play an important role in this context.” Further studies will be necessary to determine the long-term usefulness of PET imaging, genetic screening, and the two combined, the study authors concluded. By Jeff Minerd MedPage Today Staff Writer 10/10/05 The Journal of Nuclear Medicine 2005; 46:1625-1632
Word Test May Give Clues to AD - Professor Andy Ellis of the University of York in England revealed at a British Association science meeting that people in the first stages of the AD cannot write down as many animals and fruits in one-minute period as healthy individuals. He also discovered that the characteristics of the words the AD sufferers produced were different. They retained very familiar words, ones heard frequently and words learned in early, rather than late, childhood. “Just by looking at the characteristics of the words people produced you could correctly determine whether somebody came from the group of healthy controls or the AD patients,” he said. Ellis and his colleagues believe the results of the study could form the basis of a test to determine whether elderly patients are just having a “senior moment” or the memory lapse is more serious. “It is possible that exploring the characteristics of the words that are still available to them might be one of the ways one can begin to detect that something is going wrong,” said Ellis. “There is considerable value in identifying people who are beginning to show the first signs and this might be one way of doing that. The next phase of the research is to look into the possibility of making a prognostic guide,” Ellis added. By Patricia Reaney Reuters 9/6/05
More Sensitive Tests for AD - More sensitive tests may help better predict AD. Two new studies examine the effectiveness of the screenings. In the first study, from the University of Amsterdam, researchers visited older people in their homes and gave them memory tests on laptop computers. Two years later, they compared the scores of those who developed AD to those who didn’t. The tests included a screening that had participants recall five semantically related and five semantically unrelated pairs of words, a test that measured how fast participants read aloud words presented on a computer screen, and a visual association test. Researchers found those for whom “priming” information didn’t aid memory or whose learning wasn’t aided by semantic knowledge were significantly more likely to develop AD. The second study was conducted at the AD Research Center at Washington University in St. Louis. Based on results, researchers say a dichotic listening task can pick up early warning signs of AD. The task reveals how well people process information when they hear one thing in the left ear and another in the right ear. Task measurements revealed people with mild AD had a harder time switching their attention and reporting what they heard in the left ear, which sent information to the right half of the brain. The right-ear advantage increased with the severity of the dementia. People farther along in the disease found it even harder to override the usual path to process what went through the left ear to the right brain. Researchers say this confirms AD patients have problems with selective attention in the early stages. It may explain why patients start to struggle with everyday tasks, like driving, that call for processing a lot of information. Ivanhoe Newswire 9/29/05 Neuropsychology, 2005;19:629-40,687-95
Study: Weight Loss May Forewarn of AD - Seniors with unexplained weight loss may be at high risk of developing AD, a study out 9/27/05 suggests. Researcher David Bennett at Rush University Medical Center in Chicago knew that people who already have AD often lose weight, perhaps because they’re unable to shop for or prepare their own meals. The study in the September 27th issue of Neurology suggests the disease might attack brain regions that control weight years before the disease can be diagnosed. The Chicago team recruited 820 healthy Catholic nuns, brothers and priests. All were 65 or older and have been participating in the Religious Orders Study, an ongoing study on aging and AD. The researchers calculated each person’s body mass index, a formula that takes into account a person’s height and weight. Over the course of the 11-year-study, 151 people developed AD.
Height Starting weight Weight loss per year Increased risk of AD{*}
6 feet 190 lbs 7 lbs 35%
5-ft-6 150 lbs 6 lbs 35%
* Compared to a person with no weight loss
People who had lost approximately one unit of body mass index per year had a 35% greater risk of developing AD, the team found. The weight loss was not explained by dieting or other reasons. For example, a 5-foot study participant who weighed 120 pounds and who lost 5 pounds per year would run that elevated risk, says Dallas Anderson at the National Institute on Aging, which helped fund the study. The greater the weight loss, the higher the risk of AD, the research showed. An earlier study suggested that weight loss occurs several years before the symptoms of memory loss show up, Anderson says. Bennett speculates that the weight loss is not related to confusion or dementia because the Catholic nuns, priests and brothers all lived in convents or monasteries and didn’t have to cook their own meals. Instead, he says, the weight loss may be the result of damage to parts of the brain that help regulate body weight. This study suggests that seniors who have lost weight and who have no other sign of illness should be monitored for memory loss, says Sam Gandy, a spokesman for the AD Association. Identifying AD early on increasingly will become more important, Gandy says. He believes that experimental drugs might soon be available to slow down the disease. Such drugs do not yet exist, but Gandy says at-risk seniors should take charge of their affairs now before any sign of possible dementia takes hold. AD currently afflicts 4.5 million people in the USA. By Kathleen Fackelmann, USA Today 9/26/05 Neurology; Sep 2005; 65: 892-897
New Techniques May Lead to Early Detection of AD - Although AD begins long before symptoms appear, early diagnosis of AD has so far been elusive. And given that there is no cure for the disease, benefits of early detection remain questionable. The October issue of the Harvard Mental Health Letter reports on new ways to detect AD early—and reasons to want to do so. According to the Harvard Mental Health Letter, tests of cognitive function are the best way so far to predict whether healthy elderly people will develop AD. In one study, more than 80% of people who scored below a certain level on a test of delayed word recall developed AD over the next 10 years. Brain scans may also prove useful. Research suggests that they are now almost as accurate as psychological tests in predicting the course of the illness. Researchers are working on ways to detect small changes in beta-amyloid and tau protein - biological markers for the disease - in blood and spinal fluid. They’re also making progress in determining the genetic markers for AD. Even though there is currently no treatment or cure for AD, early detection is valuable, says the Harvard Mental Health Letter, for these reasons: 1) It affords people the opportunity to decide on long-term care and other important legal and family matters before the disease sets in. 2) Individuals are more likely to address other risk factors for dementia (such as vascular problems) if they learn of their risk of the disease. 3) Researchers will be able to conduct more and better clinical trials on the subject, an important step toward developing effective treatments. Newswise 9/23/05
Prevention
Green Tea Compound Stops AD in Mice - An ingredient in green tea, called epigallocatechin- 3-gallate (EGCG), has prevented AD-like brain damage in mice, researchers report. The EGCG compound decreased production of the protein beta-amyloid, which accumulates in the brains of AD patients and causes nerve damage and memory loss. “The findings suggest that a concen-trated component of green tea can decrease brain beta-amyloid plaque formation,” senior researcher Dr. Jun Tan, director of the Neuroimmunology Laboratory at the the University of South Florida’s Silver Child Development Center, said in a prepared statement. The research team worked with mice genetically programmed to develop a disease mimicking human AD. The mice received daily injections of EGCG for several months and showed as much as a 54 percent reduction in the formation of brain-clogging beta-amyloid plaques. It appears that EGCG prevents the initial process that leads to beta-amyloid formation in brain cells, the researchers said. “If beta-amyloid pathology in this AD mouse model is representative of AD pathology in humans, EGCG dietary supplementation may be effective in preventing and treating the disease,” Tan said. The researchers will next study whether multiple oral doses of EGCG improve memory loss in mice with AD. “If those studies show clear cognitive benefits, we believe clinical trials of EGCG to treat AD would be warranted,” Tan said. HealthDay News 9/21/05 Journal of Neuroscience 2005 25:8807-8814
Campus Vienna Biocenter – Progress on AD Vaccine - An innovative vaccination can significantly reduce deposits of the substances in the brain responsible for causing AD. This result was disclosed 9/15/05 by Affiris GmbH, a company located at the Campus Vienna Biocenter, Austria. The rapid progress during the pre-clinical development phase has already enabled the Vienna-based company, operating only since April 2004, to plan clinical trials for 2006. Beta-amyloids are pathological fragments of a normal brain protein. They are responsible for the development of AD, as they cause the death of brain cells. It has not yet been completely clarified whether plaque formation or the soluble beta-amyloids are the causative agents for AD. Affiris reports that it has succeeded in significantly reducing AD plaques by at least two-thirds in pre-clinical models by means of an innovative vaccine. CEO Dr. Walter Schmidt explains the important feature of the vaccination strategy: “AD is caused by a fragment of one of the ubiquitous proteins of cerebral cells. If one wants to combat AD immunologically it is essential to generate antibodies which are targeted against the beta- amyloids, but which leave the normal constituent of the cerebral cells unharmed, since the latter would induce an autoimmune disease. In keeping with this, Affiriś vaccine approach has been shown to be highly specific for beta amyloids and not to react with the normal constituent of cerebral cells.” Thus, the Affiris approach not only avoids an autoimmune disease, but also offers the advantage of targeting simultaneously both the plaques and the soluble beta-amyloid fraction. Therefore, whether the soluble or plaque forms - or both - are responsible for causing the disease is not ultimately crucial for the vaccine’s success. The additional proof that the vaccine induces antibodies, which are active against plaques in human tissue samples, and the first data collected on the toxicology profile have further contributed to built a secure basis for Affiris to schedule the first trials on patients for 2006. PR 9/15/05
Exercise in Middle Age Cuts AD Risk, Study Says - Exercising in middle age keeps the weight down and the heart healthy and can also cut the risk of suffering from AD, particularly in high- risk people, Swedish researchers say. Scientists at the Karolinska Institute in Sweden found that people in mid-life who exercised at least twice a week had about a 60 per cent lower risk of suffering from dementia than more sedentary people. “This is the first study to show this long-term relation between physical activity and dementia later in life,” Dr Miia Kivipelto, of the Aging Research Centre at the institute, said in an interview. The biggest impact was in people who had a genetic susceptibility to dementia, according to the study published in the Lancet Neurology journal. “It seems that physical activity had an even more pronounced effect among those with the susceptibility gene apoe4, the most important risk factor for AD and dementia,” Kivipelto added. Walking and cycling were the most common exercise in the study. The researchers found no link between the amount of exercise and the degree of reduced risk. They do not know exactly how exercise decreases dementia risk, but suspect it could be due to a direct effect on the brain and its messaging system and also by improving brain blood flow. Reuters 10/8/05 Lancet Neurology journal summary of the article in its corrected proof form is in the “Articles in Press” at http://www.sciencedirect.com/science?_ob=JournalURL&_cdi=7297&_auth=y&_acct=C000050221&_
version=1&_urlVersion=0&_userid=10&md5=4514c5898f120b71bfe9727759f3da09
Other Items
Early-Onset Dementia Often Misdiagnosed as AD - Research from the University of California at Los Angeles shows that early-onset dementia is often due to potentially preventable causes rather than from AD. Lead investigator Dr. Aaron M. McMurtray of UCLA presented his team’s findings Monday during the 130th annual meeting of the American Neurological Association, in San Diego, California. The study consisted of 1683 patients who were being evaluated at UCLA for declines in memory or cognition during the 4-year period between 2001 and 2004. Of these, 948 patients, or 56%, met the diagnostic criteria for dementia. The researchers divided patients into two age groups: those younger than 65 years of age and those 65 or older. Dr. McMurtray announced that patients with early-onset dementia were more likely to have a history of alcohol abuse, head trauma, HIV infection or frontotemporal lobar degeneration as the cause of their dementia. Conversely, older dementia patients more often had AD as the cause of their decline in cognitive function. “Early onset dementia, with onset in those younger than 65, is a potentially devastating problem,” Dr. McMurtray told Reuters Health. “These patients are often actively involved in holding jobs, providing for families and caring for children when the disease strikes.” “Patients with early-onset dementia are more likely to be misdiagnosed, having dementias other than AD, or have a potentially treatable or preventable etiology,” Dr. McMurtray noted. “Current work in mild cognitive impairment as a prelude to AD further highlights the importance of early diagnosis of dementing illnesses, and this is especially important at a young age. Public health measures need to address common preventable causes of dementia in this age group, including traumatic brain injury, alcohol and drug abuse and HIV infection.” By Martha Kerr Reuters Health 9/27/05
Scripps Lab Chief Explores Diabetes, AD Link - Malcolm Leissring is a principal investigator at Scripps Florida. He’s focused on a mysterious commonality between diabetes and AD. Leissring thinks the key to understanding AD lies with something called the “amyloid hypotheses,” a theory about protein fragments that appear to accumulate in the brain, clumping into plaques that bring death to brain cells like some microscopic grim reaper. Healthy people make these troublesome proteins, called beta-amyloid, but their bodies apparently dispose of them as soon as they’re made, Leissring says. In AD, he’s convinced that it’s an imbalance in the drainage system that leads to many cases of the disease. The proteins are sticky. If left in the brain, they clump together. They interfere with nerve signaling. Brain cells die. Amyloid research is moving forward in three arenas: thwarting the production of these suspect beta-amyloid proteins; preventing their aggregation into plaques; and helping the body clear them before they do damage. Leissring is betting on beta-amyloid’s clearance. Mice genetically engineered to lack one enzyme that clears beta-amyloid develop diabetes. Why? When volunteers are given high doses of insulin plus sugar, a spinal tap shows the amount of beta-amyloid in their cerebro-spinal fluid surges. Why? He thinks he’s getting some answers — and those answers bolster the amyloid hypothesis. During postdoctoral studies with his Harvard mentor, Dennis Selkoe, Leissring published a paper that appeared in the journal Neuron in 2003. It offered evidence that improving clearance of beta-amyloid could be a way to treat AD. He has a mouse brain genetically engineered to make AD plaques. It’s pockmarked with brown spots. In another a similar mouse’s brain appears uniformly gray. It’s normal. No plaques. What’s the difference? Leissring smiles. Enzymes. Cutting enzymes are the body’s equivalent of molecular scissors, catalysts that precisely cleave proteins to destroy them or make something new. One that cuts up beta-amyloid is called insulin-degrading enzyme. Beta-amyloid is the cut piece of a longer protein called amyloid precursor protein; scientists aren’t really sure what it’s supposed to do in the brain. They do know it extends beyond a neuron’s fatty membrane. Several enzymes cut it into pieces. If those pieces are the long, sticky beta-amyloid type, they must be cleared by still other enzymes. Leissring says there are many unanswered questions about insulin-degrading enzyme, in particular. He’d like to find out more about its role in diabetes. Is its improper function a cause of Type II diabetes, which usually develops in adolescence and adulthood? And in the AD arena, could he tinker with the enzyme’s molecule, make it more efficient at clearing beta-amyloid and less able to cut up insulin? If so, he might be able to make an AD drug that need not cross the difficult blood-brain barrier. That has been a stumbling block for efforts to stop production and aggregation of beta-amyloid. Overcoming that obstacle would be a huge advance. By Stacey Singer Palm Beach Post Staff Writer 9/19/05
AD Brain Can’t Block Distractions - People with AD have a harder time concentrating The brain of a person with AD may have lost the ability to block out irrelevant information and focus on the task at hand, according to a new study. Like closing your eyes when listening to music or wearing earplugs when you read, researchers say a healthy brain follows a similar strategy and automatically blocks distracting sensory stimulation to increase concentration. But their findings show this focusing process may be defective in people with AD and contribute to their disability. The results showed that healthy people deactivated the area of the brain that deals with auditory clues to complete the task, while this auditory deactivation was much less prominent in people with mild cognitive impairment and completely absent in people with AD. Researchers say the findings show that AD disorientation with their surroundings may be partially caused by their inability to focus brain activity on the relevant task. By Jennifer Warner WebMD Medical News 9/21/05 PLoS Medicine, October 2005; vol 2 DOI: 10.1371/journal.pmed.0020356