Alzheimer Related News Items

News as of 04/10/05

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Top Items

Researchers Discover Link Between Insulin and AD - Researchers at Rhode Island Hospital and Brown Medical School have discovered that insulin and its related proteins are produced in the brain, and that reduced levels of both are linked to AD. “What we found is that insulin is not just produced in the pancreas, but also in the brain. And we discovered that insulin and its growth factors, which are necessary for the survival of brain cells, contribute to the progression of AD” says senior author Suzanne M. de la Monte, a neuropathologist at Rhode Island Hospital and a professor of pathology at Brown Medical School. “This raises the possibility of a Type 3 diabetes.” It has previously been known that insulin resistance, a characteristic of diabetes, is tied to neurodegeneration. While scientists have suspected a link between diabetes and AD, this is the first study to provide evidence of that connection. The researchers determined that a drop in insulin production in the brain contributes to the degeneration of brain cells, an early symptom of AD. “These abnormalities do not correspond to Type 1 or Type 2 diabetes, but reflect a different and more complex disease process that originates in the CNS (central nervous system),” the paper states. “Now that scientists have pinpointed insulin and its growth factors as contributors to AD, this opens the way for targeted treatment to the brain and changes the way we view AD,” de la Monte says. In an accompanying review article, de la Monte and accompanying author Jack Wands, MD, of Rhode Island Hospital and Brown Medical School, write that “there is a genuine need for thorough and comprehensive study of the neuropathological changes associated with diabetes mellitus, in the presence or absence of superimposed AD or vascular dementia.” PR 3/7/05 Journal of Alzheimer’s Disease 7, 1, 45-61 and 63-80 March 2005

Computer Test Accurately Detects Early AD - Researchers have developed a more accurate version of a standard test to detect dementia and cognitive impairment that takes only about 10 minutes to administer. The standard scoring method for dementia, known as the “National Institute of Aging’s Consortium to Establish a Registry for AD 10-word list” (CWL), consists of three immediate-recall trials of a 10-word list, followed by an interference task, and then a delayed-recall trial of the word list. “In the traditional scoring and interpretation, only the total score from the fourth trial is usually used,” lead author Dr. William R. Shankle explained to Reuters Health. However, much more information can be gleaned from analyzing the patterns of words recalled based on their placement in the list. “The method we describe -- the mental skills test -- uses the individual responses to every item in all four trials to come up with an answer,” the researcher added. The mental skills test takes about 10 minutes to administer online. Once the answers are submitted, a formula is used to calculate the final score that within seconds “indicates if a person is impaired or not with an overall accuracy 97 percent,” Shankle said. By Karla Gale Reuters Health 3/21/05 Proceedings of the National Academy of Science, 102, 13, 4919-4924 March 29, 2005

AD Drug to Carry New Warning Label - Johnson & Johnson has added a new warning to the label of its AD treatment, Reminyl, about two studies that included the deaths of 13 patients who took the drug and one who took a placebo, the company and U.S. regulators said 4/1/05. The deaths “were due to various causes that could be expected in the elderly population” such as heart attacks and strokes, and the findings were “highly discrepant” with other studies of Reminyl, the company said in a letter to physicians. The two studies involving more than 2,000 patients were testing Reminyl as a treatment for mild cognitive impairment, a less severe condition than AD. The rate of deaths in patients who got a placebo was lower in the mild cognitive impairment trials than in trials of AD patients, Johnson & Johnson said. The information about the deaths, which the company disclosed in January, was added to the “precautions” section of the Reminyl label, a less severe alert than other prescription drug warnings. Reuters 4/1/05

Osteoporosis Drug May Help Preserve Memory - The osteoporosis drug Evista (raloxifene) may also help postmenopausal women avoid memory problems. Evista is one of several drugs used to prevent and treat osteoporosis, in which bones become dangerously thin and more likely to fracture. Women taking 120 milligrams of Evista for three years had a 33% lower risk of a condition called mild cognitive impairment. Women taking a lower dose of Evista (60 milligrams daily) saw no protection. In mild cognitive impairment there are subtle but measurable memory problems. This condition often progresses to AD. The results need confirmation, say the researchers. They’re not sure if the mental benefits extend to men, younger or nonwhite women, or postmenopausal women without osteoporosis. The researchers call for longer trials and studies of women at high risk for AD or cognitive impairment. WebMD Medical News 4/8/05 The American Journal of Psychiatry’s 162:683-690, April 2005

Fooling AD With a Decoy Drug - Scientists are working on a new drug that tricks toxic brain proteins linked to AD by sidelining them before they form plaques and tangles that burden patients’ brains. “This work may lead to the development of new tools and/or therapeutics for use in AD,” says researcher Theresa Good, PhD, a chemist with the University of Maryland-Baltimore County. Good says the drug has fared well in lab tests on cells, but it hasn’t yet been tried in animals or people. “Of course, there is a long way to go before one can use these molecules in the human body,” she says. But so far, lab tests on cells look promising, she notes. The drug is built to attract beta-amyloid proteins and hold on tight. That way, the proteins don’t have the chance to form senile plaque. The drug could also serve as a marker for the harmful beta-amyloid proteins, perhaps leading to an AD test for living patients. By Miranda Hitti WebMD Medical News 3/17/05 Presented at ACS Meeting San Diegeo March 12-16, 2005

Genes & Genetic Issues

Brain’s Own Stem Cells Might Fight AD - The activation of dormant stem cells in the patient’s own brain could someday allow doctors to re-grow lost cells without resorting to surgery, and in ways that target exactly those areas of the brain -- and specific types of cells -- damaged by disease. “We’re developing maps so that we’ll know exactly which stem cells give rise to every cell subtype in the brain,” explained Dr. Mark F. Mehler, chairman of the department of neurology at Albert Einstein College of Medicine, and neurologist-in-chief at Montefiore Medical Center, New York City. “That means, we’ll be able to say the equivalent of, ‘OK, in sector three of sub-zone 7, we need to activate that cell.’ And not only activate it, but activate it in a specific way,” he added. The technique -- still years away from clinical trials -- is called endogenous (meaning sourced from the patient) stem cell activation. Residual amounts of these regenerative cells exist throughout the body. According to Mehler, about 0.3 percent of brain cells may be dormant stem cells. Just why they so often remain dormant -- even when the brain experiences injury -- remains a mystery. According to Mehler, the Holy Grail of endogenous stem cell activation is a non-invasive means of introducing genes or chemicals into the brain that are targeted to only re-grow those cells lost to AD or other brain diseases. The technique would also get around so many of the problems inherent in stem cell transplants -- from issues of immune system rejection to the ethical concerns that dog the use of embryonic cells. However, another expert cautioned the success of this strategy is far from assured. According to Mehler, a clinical trial may take place in the not-so-distant future. Using safe, noninvasive infusion techniques already used in cancer chemotherapy, his team plans to use growth factors to jump-start sleepy brain stem cells in human subjects, sometime over the next five years. “It would be even better to do this using gene manipulation, because it would be even less invasive,” he said, but gene therapy remains a more distant goal. Still, treatments that rely on the brain’s own secret store of stem cells might come sooner than anyone can imagine, Mehler said. By E.J. Mundell HealthDay Reporter 3/14/05

House Leaders Agree to Vote On Relaxing Stem Cell Limits - The House leadership has agreed to allow a floor vote on a bill that would loosen the restrictions on human embryonic stem cell research imposed by President Bush in 2001, according to members of Congress and others privy to the arrangement. The vote, expected to take place within the next two to three months, would be the first of its kind on the politically charged topic since Bush declared much of the research off-limits to federal funding. The cells show promise as treatments for many diseases but have stirred intense controversy because they are retrieved from human embryos, which are destroyed in the process. “We’re very pleased,” said Rep. Michael N. Castle (R-Del.), a supporter of policy change who helped broker the deal. “This is an indication they recognize the importance of this.” By Rick Weiss Washington Post Staff Writer 3/25/05

Changes Are Weighed on Stem Cells - With some Republicans pressing to loosen President Bush’s restrictions on federal financing for embryonic stem cell research, the director of the National Institutes of Health said 4/6/05 that there is “mounting evidence” that such a policy change would benefit science, and other top N.I.H. officials echoed his assessment. Dr. Elias Zerhouni, the health institutes’ director, said he was not advocating a policy change and acknowledged the research raised moral concerns. But in testimony to a panel of senators, he made clear that scientists believe the current rules, which limit federal financing to a certain number of colonies, or lines, of embryonic stem cells, are hindering scientific progress. “From a scientific standpoint, there is no doubt that many scientists will tell you that there are questions they would like to be able to address, that more lines, such as the lines, for example, that harbor specific genetic defects, would be helpful to them,” Dr. Zerhouni said in an interview after the hearing, adding, “There are areas of research that you could pursue.” By Sheryl Gay Stolberg NY Times 4/7/05

Massachusetts House Passes Law Expanding Use of Stem Cells - The Massachusetts House passed a bill 3/31/05 that would give scientists more freedom to conduct embryonic stem cell research in the state. The House voted 117 to 37 to approve the measure, giving it enough votes to override an expected veto by Gov. Mitt Romney (R). The Senate had overwhelmingly approved the bill on 3/30/05. The measure would allow scientists to create cloned embryos and extract their stem cells for research into the treatment and cure of diabetes, Parkinson’s disease, spinal cord injuries and other conditions. Under current state law, scientists interested in conducting stem cell research first need the approval of the local district attorney. The bill would remove that requirement, give the state Health Department some regulatory controls and ban cloning for reproductive purposes. AP 4/4/05

Testing

AD Plaques Revealed in Living Brains - The characteristic plaques of AD have been made visible in the brains of living mice. The non-invasive technique should work in people too, and could improve diagnosis and make it easier to measure the effects of potential treatments. Amyloid plaques do not normally show up in MRI scans. There has been some success with PET scans, but the resolution is not good, it is extremely expensive and it exposes people to radiation. Now Takaomi Saido’s team at the Riken Brain Science Institute in Wako, Japan, has developed a non-toxic tracer that attaches itself to the plaques in the brain. The tracer is made by combining a fluorine isotope that shows up in MRI scans with a compound that binds to amyloid. Tests on mice show that the tracer is non-toxic and that only low doses are needed to reveal plaques in their brains). Saido’s team has also confirmed that the tracer binds to amyloid in human brain tissue, though it has not yet been tested on living people. New Scientist 3/19/05 Nature Neuroscience 8, 527-533 (2005)

Prevention

Study: Large Vitamin E Doses Risky - Large doses of vitamin E -- widely touted as an elixir of youth -- do not protect against heart attacks and cancer and might actually raise the risk of heart failure in people with diabetes or clogged arteries, a study found. The study, published in the Journal of the American Medical Association, is just the latest to cast doubt on the safety and effectiveness of vitamin E supplements and other antioxidants. The study involving 7,030 patients with diabetes or cardiovascular disease other than heart failure was designed to examine whether vitamin E pills protect against heart attacks and cancer. It found no benefit against those conditions. But the heart failure finding was unexpected and should prompt more research to confirm the results, said Dr. Eva Lonn, a McMaster University cardiology professor who led the study. Lonn said it is unclear how vitamin E pills might be linked with heart failure, but she theorized that high doses might disturb the balance of beneficial, naturally occurring anti-oxidants. Patients 55 and older who took about 400 milligrams of vitamin E every day for about seven years on average were 13 percent more likely to develop heart failure than those on dummy pills. Heart failure was diagnosed in 641 vitamin E patients, compared with 578 patients in the placebo group. The dosage was typical of vitamin E pills widely available at health food stores and pharmacies but well above the recommended 15 milligrams daily for adults, which can be obtained from food. Lonn said the findings pertain only to vitamin pills, not a diet containing vitamin E-rich foods, including nuts and leafy green vegetables. “I don’t think our study rules out in any way that a balanced diet rich in antioxidants would actually be beneficial,” she said. The study “effectively closes the door” on the theory that high doses have a major protective effect against cancer and narrowing of the arteries, University of Washington health specialists Dr. B. Greg Brown and John Crowley said in an editorial. AP 3/15/05 JAMA 2005;293:1338-1347

Fatty Acid-rich Diet May Block AD - Consuming a diet rich in the omega-3 fatty acid docosahexanoic acid (DHA) may help prevent or treat AD, findings from an animal study suggest. In the study mice that ate DHA-enriched chow showed less beta-amyloid build-up in the brain than mice fed regular chow. Beta-amyloid is a protein that forms the characteristic brain plaques seen in patients with AD. “These results suggest that dietary DHA could be protective against beta-amyloid production, accumulation, and potential downstream toxicity,” senior author Dr. Greg M. Cole, from the University of California at Los Angeles, and colleagues note. Research has linked high levels of DHA in the diet with a reduced risk of AD. Still, the studies have shown an association, but don’t prove that eating a diet high in DHA actually reduces amyloid levels and prevents AD. To show this, animal studies are often needed. Cole’s team used a mouse model of AD and fed the animals low- or high-DHA chow or regular chow. The animals were fed the assigned diet until 22.5 months of age, at which point brain tissue was obtained and tested for amyloid build-up. The high-DHA diet reduced total amyloid level by 70 percent compared with the other diets, the investigators report. Moreover, brain plaques were reduced by 40.3 percent. Several studies are currently underway to determine if fatty acids like DHA offer any benefits for patients with mild-to-moderate AD, the authors add. Reuters Health 3/22/05 The Journal of Neuroscience, March 23, 2005, 25(12):3032-3040; doi:10.1523/JNEUROSCI.4225-04.2005

Fend Off Dementia with Sex, Crosswords and a Run - Sex, cryptic crosswords and a good run could help ward off dementia and other degenerative conditions by stimulating new brain cells, an Australian researcher said on 4/7/05. Perry Bartlett, a professor at the University of Queensland’s Brain Institute, said mental and physical exercise helped create and nurture new nerve cells in the brain, keeping it functional and warding off diseases such as AD and Parkinson’s. “Perhaps one should run a long distance and do the cryptic crossword,” Bartlett told Australian radio. He said a chemical called prolactin appeared to promote new cells in the brain and could be found in high levels in pregnant women. “Prolactin levels also go up during sex as well. So one could think of a number of more entertaining activities than running in order to regulate the production of nerve cells,” Bartlett said. Reuters 4/7/05

Depression May Up Risk of Dementia in Men - Men with a history of depression long before the onset of any memory or other cognitive problems have a substantially higher risk of developing dementia, especially AD, later in life, a study indicates. This risk is not observed in women. Dr. Gloria Dal Forno, of University Campus BioMedico and Associazione Fatebenefratelli per la Ricerca, Rome, Italy, and colleagues examined the association between premorbid symptoms of depression and the development of dementia and AD over a period of 14 years in 1357 subjects enrolled in a study on aging. The risk of dementia, especially AD, was significantly increased with premorbid depressive symptoms only in men. The risk was approximately two times greater in those with a history of depression than for those without a history of depression, and was independent of the presence of vascular disease. “The prevalence and clinical manifestations of both AD and depression differ in men and women,” Dal Forno noted in an interview with Reuters Health. “We know that male and female brains have anatomical and functional differences and are exposed differently to sex hormones throughout life, hormones known to have effects on both depression and AD,” she noted. “As a consequence, male and female brains might react to conditions causing or enhancing a disease quite differently, which seems to be precisely what we found in this investigation.” Given the prevalence of depression and increasing longevity worldwide, “clearly the public health and economic implications are significant,” the researcher added. Furthermore, “Prevention of depressive disorders and aggressive as well as long-term treatment of depression may impact on the epidemiology of dementia,” she added. “This is particularly relevant in men since they generally are less likely to admit to symptoms of depression and to seek treatment.” By Michelle Rizzo Reuters Health 3/24/05 Annals of Neurology 57, 3, 381-387 March, 2005

Other Items

OHSU Researchers Demonstrate How AD Impacts Important Brain Cell Function - Scientist at the Neurological Sciences Institute at Oregon Health & Science University have demonstrated how proteins involved in brain cell communications, called synaptic proteins, decrease in the brains of AD patients when compared to healthy brains from people in the same age range. “We found that the decrease of synaptic protein levels in the frontal cortex of the brains of AD patients was more severe than in other portions of the brain,” explained P. Hemachandra Reddy, Ph.D. “Because the frontal cortex is home to important brain functions such as reasoning, planning, and abstract thought – all affected by AD - this finding appears to be significant. Furthermore, we noticed that synaptic protein levels were even lower in the brains of patients in the early stages of AD. This suggests to us that the loss of these important proteins happens very early in the disease process.” One possible reason for the reduction of synaptic proteins is mitochondrial dysfunction, a well-documented occurrence in AD. “What this study helps demonstrate is that the decrease of synaptic proteins is an early and important impact of AD that likely impacts one of the brains most important functions - communication,” added Reddy. “Moreover we now know much more about where these changes are taking place and what appear to be the proteins most severely impacted to the disease.” PR 4/7/05 Journal of Alzheimer’s Disease vol. 7, No. 2 in press Abstract at http://www.j-alz.com/issues/7/vol7-2.html

AD Theory Launches Scripps Lectures - Down syndrome and AD may share a common origin: too many copies of the 21st chromosome, said Huntington Potter, chief executive officer of the Johnnie B. Byrd, Sr. Alzheimer’s Center & Research Institute in Tampa on 3/28/05. This is an unconventional theory about the cause of AD. One of his partners, based in Finland, has identified a molecule that seems to successfully disrupt the assembly of the brain plaques seen in both AD and Down syndrome. The challenge will be perfecting that molecule so it can be made into a drug which can be absorbed by the body and used within the brain, he said. The link Potter has described between AD and inflammation - whether caused by disease or head injury - is more widely accepted than his theory that Down syndrome and AD share a common cause. But Potter feels certain he’s right about this one, too. “It’s a curious fact that every single Down syndrome patient develops AD by age 30 or 40. Now some of the individuals may not develop the same memory deficit, but from a biochemical and pathological point of view, their brains look like the AD brain,” Potter said. His group and others have looked at the chromosomes of AD patients and discovered that an abnormally high percentage of them have three copies of the 21st, just like Down syndrome patients. By Stacey Singer Palm Beach Post Staff Writer 3/28/05

Blue-Green Algal Links to AD-Like Neurological Disease - An international team of researchers, including scientists from the University of Dundee have announced that cyanobacteria (blue-green algae) found throughout the world may produce a toxin linked to certain types of neurological disease. Researchers have previously proposed a link between beta-methyl-amino-alanine (BMAA), a neurotoxic amino acid found in cyanobacteria and an AD-like neurodegenerative disease suffered by the Chamorro people on Guam in the Pacific. The Chamorro people eat the seeds from cycads, plants found only in warm regions of the world which were found to produce BMAA. Dr. Paul Cox, Director of the Institute for Ethnomedicine of the National Tropical Botanical Garden in Hawaii, and his colleagues found that BMAA is produced by a cyanobacterium resident in special roots of the cycad. Interest increased when BMAA was found in brain tissues of several AD patients in Canada. The study raises questions, the scientists caution, “Whilst BMAA is neurotoxic, the nature of the association with human neurological disease remains uncertain” says Codd. “However we now know that BMAA is widely produced by cyanobacteria from throughout the world, in addition to a rather specialist cyanobacterium on a small Pacific island. This indicates that human exposure to BMAA may also occur more widely and that BMAA should be monitored in water resources, including reservoirs, if they contain cyanobacteria. Now that we know about BMAA in cyanobacteria, steps can be taken to reduce the risks to health which the substance may present.” Medical News Today 4/10/05 to be published in Proceedings of the National Academy of Sciences

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