Impaired clearance, not overproduction of toxic proteins, may underlie Alzheimer’s disease
09 December 2010
In Alzheimer's disease, a protein fragment called beta-amyloid accumulates at abnormally high levels in the brain. Now researchers funded by the National Institutes of Health have found that in the most common, late-onset form of Alzheimer’s disease, beta-amyloid is produced in the brain at a normal rate but is not cleared, or removed from the brain, efficiently. In addition to improving the understanding of what pathways are most important in development of Alzheimer's pathology, these findings may one day lead to improved biomarker measures for early diagnosis as well as a new approach to treating this devastating disorder.
Many believe that accumulation of abnormal levels of beta-amyloid in the brain initiates a cascade of events leading to the death of brain cells and ultimately to dementia. In the rare, early-onset forms of Alzheimer's that are linked to genetic mutations there is a marked increase in beta-amyloid production. In the more common, late-onset form of Alzheimer's, the mechanisms leading to increased beta-amyloid levels are not well understood.
The study, published in Science, was led by senior author Randall Bateman, M.D., an assistant professor of neurology at Washington University in St. Louis. Dr. Bateman and his colleagues previously reported an innovative procedure to measure beta-amyloid levels over time in cerebrospinal fluid (CSF) — the fluid that bathes the brain. In the new study, the researchers used that procedure to measure beta-amyloid production and clearance rates in study volunteers with Alzheimer’s disease and in age-matched volunteers free of the disease.
"These findings may help point us toward better diagnostic tests and effective therapies. The next question is what is causing the decreased clearance rate," said Dr. Bateman.
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