all Alzheimer's disease stories

Scientists isolate a toxic key to Alzheimer's disease in human brains

404132862 — Mon, 23 Jun 2008 20:23:16 -0400

Scientists have long questioned whether the abundant amounts of amyloid plaques found in the brains of patients with Alzheimer's actually caused the neurological disease or were a by-product of its progress. Now, using new research techniques, scientists have shown that a two-molecule aggregate (or dimer) of beta-amyloid protein fragments may play a role in initiating the disease.

Even in healthy elderly, brain systems become less coordinated

404132862 — Wed, 05 Dec 2007 16:31:14 -0500

Some brain systems become less coordinated with age even in the absence of Alzheimer’s disease, according to a new study from Harvard University. The results help to explain why advanced age is often accompanied by a loss of mental agility, even in an otherwise healthy individual.

Brain implants relieve Alzheimer’s damage

50443248 — Mon, 01 Oct 2007 15:53:35 -0400

Genetically engineered cells implanted in mice have cleared away toxic plaques associated with Alzheimer’s disease.

The animals were sickened with a human gene that caused them to develop, at an accelerated rate, the disease that robs millions of elderly people of their memories. After receiving the doctored cells, the brain-muddling plaques melted away. If this works in humans, old age could be a much happier time of life.

Alzheimer’s involves a protein called amyloid-beta, which makes up gooey clots or plaques that form in the brain. These toxic clumps, along with accessory tangled fibers, kill brain cells and interfere with memory and thinking. The situation has been compared to a build-up of cholesterol in coronary arteries.

Finding the start of Alzheimer's disease

Tue, 10 Jul 2007 15:46:24 -0400

Faces are hard to remember. Even harder are the names that go with them. It’s one of the most common problems people face as they get older.

In puzzling over why that is, Reisa Sperling and her colleagues at Harvard Medical School have discovered startling things about how memories are made and why people lose them, particularly those on the way to Alzheimer’s disease.

“Names and faces are so difficult to put together because there’s no obvious connection between them,” says Sperling, who is an associate professor of neurology. “There’s no ‘Bill look,’ or ‘Mary face.’”

Important signal uncovered in brain development

Thu, 12 Jul 2007 10:51:55 -0400

Nobody has counted them, but the best estimates put the number of human brain cells in the trillions. The best known among them, called neurons, do the heavy thinking and remembering. Each of these cells can connect to 10 or more others, forming a vast network of feelings, thoughts, memories, prejudices, and PINS.

But neurons don't do their jobs alone. They are supported and regulated by an immense system of star cells, called astrocytes, because of their shape. New research has discovered how these stars are born. The discovery also hints at how defective astrocytes may contribute to Alzheimer's disease.

It has been known for years that both neurons and astrocytes come from the same brain stem cells. But how do these cells know whether and when to make one or the other?

Potential Alzheimer's vaccine improves learning and memory deficits in mice

70652986 — Mon, 26 Mar 2007 06:27:13 -0400

Researchers have found that a vaccine for Alzheimer's disease improves learning and memory deficits in mice.

"Our findings show promise for a potentially safer and more effective Alzheimer's vaccine in humans," says senior researcher and Harvard Medical School associate professor Cynthia Lemere. Lemere and colleagues at Brigham and Women's Hospital report combined immunological, neuropathological, and behavioral benefits of the vaccine in mice.

"Next, we plan to further refine our novel vaccine and prepare for possible human trials," she says.

The study appears in the May 3, 2006 issue of The Journal of Neuroscience.

Enzyme key in preventing Alzheimer's onset

70652986 — Mon, 26 Mar 2007 07:10:50 -0400

A new discovery has found that Pin1, an enzyme previously shown to prevent the formation of the tangle-like lesions found in the brains of Alzheimer's disease patients, also plays a pivotal role in guarding against the development of amyloid peptide plaques, the second brain lesion that characterizes Alzheimer's.

These new findings, shown in an animal study, provide further evidence that Pin1 (prolyl isomerase) is essential to protect individuals from age-related neurodegeneration and for the first time establish a direct link between amyloid plaques and tau tangles, the two abnormal structures that are considered the pathological hallmarks of this devastating disease. Led by researchers at Beth Israel Deaconess Medical Center (BIDMC) and Harvard Medical School, the study appears in the March 23, 2006 issue of the journal Nature.

"A century ago, in 1906, the German doctor Alois Alzheimer first observed an abundance of these plaques and tangles in the brains of Alzheimer's patients," explains the study's senior author, Kun Ping Lu, MD, PhD, an investigator in the Division of Cancer Cell Biology at BIDMC and associate professor of medicine at Harvard Medical School.

"Throughout the years, intensive studies have been done to find out the causes of these two major lesions, but the exact relationship between the two has remained controversial and elusive," he adds. "Coupled with recent independent studies showing that genetic changes in the human Pin1 gene are associated with reduced Pin1 protein levels as well as an increased risk of Alzheimer's disease, these new results suggest that lack of sufficient Pin1 enzyme may be a key culprit in the onset of Alzheimer's disease."

Lu, together with Tony Hunter from the Salk Institute, first identified the Pin1 enzyme in 1995. Eight years later, in 2003, Lu and his colleagues demonstrated that Pin1 promoted dephosphorylation of tau, thereby 'detangling' the protein which had become knotted and overburdened with excess phosphate molecules. They also confirmed that when Pin1 was missing, neurons in the regions of the brain responsible for memory would collapse under the weight of the tau protein tangles, ultimately leading to age-dependent neurodegeneration.

In this new study, Lu and his coauthors hypothesized that Pin1 might be acting in a similar fashion to regulate APP (amyloid precursor protein) cleavage and amyloid beta production, thereby preventing the formation of plaques.

This study was funded in part by grants from the National Institutes of Health, the National Science Foundation and the Taiwan National Science Council.

Work progressing on Alzheimer's, but too slowly

50443248 — Fri, 20 Jul 2007 11:59:43 -0400

Actor David Hyde Pierce made an emotional plea for increased activism around Alzheimer's disease Monday (Oct. 17), saying that federal funding has leveled off despite scientific progress in understanding and treating the disease in the last 15 years.
Pierce, a member of the Alzheimer's Association's National Board, watched both his father and grandfather deteriorate and die from the disease, and watched both his mother and grandmother wither under the strain of care-giving and die of other causes.

Vaccine may clear Alzheimer's brain plaques

70652986 — Mon, 26 Mar 2007 05:41:07 -0400

While there is still no consensus about the role of waxy amyloid plaques that fill the brains of Alzheimer's patients, many in the field believe they are a root cause of neurodegeneration and that clearing them may improve the cognitive function of patients. A major strategy has been to remove amyloid-beta by creating antibodies against it. But trials for an amyloid-beta vaccine were halted in 2003 when 6 percent of the patients developed life- threatening encephalitis. Since then, two follow-up studies provided some evidence that patients did benefit, raising hopes that a vaccine may work if side effects are limited. Another trial is under way to see if delivering amyloid-beta antibodies, rather than the peptide itself, can be effective and safer.

In the September 2005 Journal of Clinical Investigation, a team led by Howard Weiner, the Robert L. Kroc professor of neurology at Harvard Medical School and Brigham and Women's Hospital, unveiled another vaccine strategy for Alzheimer's disease that clears the build-up of amyloid plaques in a mouse model. The new strategy triggers cells of the immune system to gobble up amyloid-beta, sidestepping antibodies completely. It is delivered as a simple nasal spray, and consists of two FDA-approved drugs already in use for other conditions.

The vaccine emerged from a fortuitous discovery during an investigation of the role of the immune system in Alzheimer's. After the problems with the amyloid-beta vaccine, Weiner worked with postdoctoral fellow Dan Frenkel and Ruth Maron, assistant professor of neurology at BWH, to investigate the relationship between Alzheimer's and an overactive immune system that would produce encephalitis.

Compound traces brain plaques in real time

70652986 — Mon, 26 Mar 2007 05:32:00 -0400

Alzheimer's disease is notoriously difficult to diagnose. Though sophisticated functional and cognitive tests can help, they often fail to distinguish between Alzheimer's and other non-amyloid-based dementias, particularly frontotemporal dementia. The ability to measure plaques in vivo would not only provide clinicians with an immediate and reliable diagnosis, but over time would allow them to gauge how the disease is progressing. Positron emission tomography (PET) may be a window into the brain for neurologists. Harvard researchers have described how a compound, called Pittsburgh compound B (PIB), can be tracked by PET, a technique that may soon be used to diagnose and monitor Alzheimer's disease in humans. The technique is described in the Sept. 29, 2003 online edition of Proceedings of the National Academy of Sciences by Assistant Professor of Neurology Brian Bacskai and the John B. Penney Jr. Professor of Neurology Bradley Hyman, both at Harvard Medical School and Massachusetts General Hospital.

Early molecule fingered as an Alzheimer's cause

70652986 — Mon, 26 Mar 2007 05:31:51 -0400

"The way we look at it, Alzheimer's disease is really cancer of the brain," says Rachael Neve, Harvard Medical School associate professor of psychiatry at McLean Hospital. "But neurons cannot divide and form tumors so they undergo apoptosis (cell death) instead." Neve; Donna McPhie, Harvard Medical School instructor in psychiatry; and their colleagues show in a study appearing in the July 30, 2003 Journal of Neuroscience that a substance known as amyloid precursor protein, or APP, is implicated in Alzheimer's disease. The study shows not only that APP kills neurons but also how it carries out its killing. More important, they provide a new and surprising conception of the nature of Alzheimer's disease, one that could lead to a fundamental shift in how the disease is viewed and treated.

Alzheimer's disease: New theory on how it damages brain

70652986 — Mon, 26 Mar 2007 05:28:34 -0400

Studies have shown that the buildup in the brain of certain toxic proteins, called amyloids, leads to the emergence of the symptoms of Alzheimer's disease. Research has traditionally focused on how to eliminate or lower the levels of these proteins in the brain as a potential treatment for the disease. But now researchers believe that the memory loss associated with the disease begins long before protein deposits collect in the brain, and that a new understanding of how the disease progresses may have an important impact on how Alzheimer's is treated in the future.

Alzheimer's-associated enzyme elevated in key brain areas

70652986 — Mon, 26 Mar 2007 05:25:09 -0400

A research report that appears in the September 2002 issue of the journal Archives of Neurology may improve understanding of the most common form of Alzheimer's disease. "Our key finding is that beta-secretase activity -- the efficiency of how the enzyme works -- is increased in Alzheimer's diseased brains specifically in those areas affected by the disease," says Michael Irizarry, of the Alzheimer's Disease Research Unit in the Massachusetts Genearl Hospital Department of Neurology and the paper's senior author. "The beta-secretase increase persists and even increases throughout the duration of the illness, which may make this enzyme a useful target for treatment, even late in the disease." In Alzheimer's, amyloid-beta is released when the large APP molecule is clipped in one location by beta-secretase and in another spot by an enzyme called gamma-secretase. The amyloid-beta fragments collect in plaques -- one of the classic brain abnormalities of Alzheimer's disease -- which significant evidence suggests are toxic to brain cells. The research was supported by grants from the National Institutes of Health, the Walters Family Foundation and Takeda Chemical Industries.

Lack of protein ApoE in brain may raise Alzheimer's risk

70652986 — Mon, 26 Mar 2007 05:18:29 -0400

Brain cells are protected from possible contamination by substances in circulating blood by what is known as "the blood-brain barrier." Researchers have many questions about precisely how this protective mechanism works. Recently, Harvard Medical Sschool researchers identified a protein that supports the blood-brain barrier. When a molecule, apolipoprotein E (apoE), is absent, the barrier becomes especially porous, making the brain vulnerable to trauma and possibly Alzheimer's disease. Denisa Wagner, Harvard Medical School professor of pathology at the Center for Blood Research and senior author of the study, "wondered whether apoE might be important for the integrity of the brain's vasculature." In a study with mice, her research team found that it was. According to Wagner, this study, published in the December 2001 issue of Molecular Medicine, and two others published recently suggest links between apoE, an impaired blood-brain barrier, and Alzheimer's. Major risk factors for the disease, such as brain injury, age, and high cholesterol, are precisely those that aggravate the increase in blood-brain barrier permeability associated with apoE deficiency.

Study shows strong public interest in genetic testing for Alzheimer's disease

70652986 — Mon, 26 Mar 2007 05:15:28 -0400

A genetic test to determine a person's chance of getting Alzheimer's disease is still hypothetical. But scientists are getting closer and closer to being able to determine who is likely to get the disease. A study by Harvard researchers and their colleagues found that, once such a genetic test is developed, approximately 80 percent of adults would take it, if they could be assured of its accuracy. Willingness to take an accurate test was strong across all age groups who were polled in a random telephone survey. But willingness to take the test falls to 45 percent if the test has a one in 10 chance of being wrong. The findings were made by Peter Neumann and James Hammitt at the Harvard Center for Risk Analysis, part of the Harvard School of Public Health, as well as Kenneth Kosik, of Harvard Medical School, and Howard Fillit and colleagues at the Institute for the Study of Aging. The study was funded by a grant from the Institute for the Study of Aging, a non-profit research institute established by the Estee Lauder Trust and dedicated to research on cognitive aging and Alzheimer's disease.