Mar 2, 2010

New Look at Alzheimer’s Associated Protein Amyloid-Beta, May Have Beneficial Function as Part of the Innate Immune System

Unlocking the Mystery Could Be the Key to Finding the Cure.

Alzheimer's Reading Room

The Amyloid-beta protein is a key contributor to Alzheimer’s pathology and has been thought to be just a byproduct of abnormal processes within the brain. But researchers supported by Cure Alzheimer’s Fund (CAF) at Massachusetts General Hospital in Boston have shown that the protein may be part of the body’s natural defense against infection.

Published in the March issue of the open-access journal PLoS One, the research of Dr. Rudolph Tanzi, chairman of CAF’s research consortium and director of the Mass. General Genetics and Aging Research Unit, Dr. Robert Moir of Mass General Hospital’s Genetics and Aging Research Unit and their colleagues, could also aid in explaining the connection between Alzheimer’s and previous infection and trauma to the brain, such as head injuries and strokes. Earlier work by Tanzi and colleagues and others has indicated that A-beta responds to such occurrences with excess production and accumulation of the protein in the brain.
“These data change the way we look at Abeta. For years we thought that A-beta was just metabolic garbage produced as a byproduct of other processes within the brain, but these data suggest it is a normal component of the brain’s innate immune system”, says Dr. Tanzi. Knowing this could lead to innovative preventive treatments for Alzheimer’s disease. “If we can manage the production of A-beta in the brain’s innate immune system triggered by combinations of genetics and environmental factors, we may be able to lower the risk for this devastating disease,” said Tanzi. “Finding the catalyst for the production of excessive A-beta aggregation could lead to finding ways of controlling it, whether by medication or immunization.”

Co-senior author of the PLoS One paper, Robert Moir, PhD, observed similarities between A-beta and peptides known to be part of the body’s innate defense system. He and his colleagues tested A-beta against known a antimicrobial agent to compare their ability to suppress the growth of such microbial pathogens as Candida albicans (yeast). Brain tissue from Alzheimer’s patients and age-matched controls was then tested for antimicrobial activity.

The tissue samples were taken from the temporal lobe of the brain, where amyloid plaques are primarily found. The experiment showed significant antimicrobial activity in Alzheimer’s patients, but much less from the control group. Patient samples with higher levels of A-beta demonstrated stronger antimicrobial strength. Conversely, antibodies that reduced the presence of A-beta proved to hinder antimicrobial strength in patient samples.

More research revealed that tissue from the cerebellum, an area with known low A-beta levels, did not suppress Candida growth from either Alzheimer’s patients or controls.

This research suggests that excess accumulation of A-beta, which in its aggregated or oligomeric form is toxic to neurons, can be initiated by the innate immune system in response to various kinds of infection as well as by genetic predisposition and/or such events as head trauma or stroke. It is important to note that several of the Alzheimer’s candidate genes recently
identified by Tanzi and others play a role in the innate immune system.

“This is the kind of creative research that often does not get federal funding”, said Tim Armour, President and CEO of Cure Alzheimer’s Fund. “We are thrilled that this high risk investment has paid off in truly breakthrough findings that open up new pathways to prevention of this terrible disease.”

The March 3 PLoS paper, “The Alzheimer’s Disease-Associated Amyloid-beta Protein is an Antimicrobial Peptide” was supported exclusively by grants from Cure Alzheimer’s Fund. Co-authors of the study include Stephanie J. Soscia, MassGeneral Institute of Neurodegenerative Medicine (MGH-MIND) and Boston University School of Medicine; James E. Kirby, Beth Israel Deaconess Medical Center; Kevin Washicosky, Stephanie M. Tucker of MGH-Mind; Marin Ingelsson of
Uppsala University, Sweden; Bradley Hyman, MGH- MIND; Mark A. Burton and Lee Goldstein, Boston University; Scott Duong, Beth Israel Medical Center; Rudolph E. Tanzi and Robert D. Moir of MGH-Mind and Harvard Medical School.

About Cure Alzheimer's Fund

Cure Alzheimer's Fund™ is a 501c3 public charity whose mission is to fund research with the highest probability of slowing, stopping or reversing Alzheimer's disease. Cure Alzheimer’s Fund is characterized by a venture approach to philanthropy, which targets funding to specific
research objectives. All expenses and overhead is paid for by its founders and all contributions go directly to research. The Foundation has no financial or intellectual property interest in the research funded, and will make known the results of all funded research as soon as possible. Cure Alzheimer’s Fund is a national organization with offices in Boston and Pittsburgh.
For more information, visit

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Bob DeMarco is the Founder of the Alzheimer's Reading Room and an X Wall Street executive turned full time Alzheimer's caregiver. The blog contains more than 2,310 articles with more than 285,100 links on the Internet. Bob resides in Delray Beach, FL.

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