Accumulation of Beta-Amyloid in Alzheimers the Result of Impaired Clearance
An accumulation of beta-amyloid in the brain is one of the hallmark features of Alzheimer’s disease, but scientists haven’t been entirely sure of the process by which this happens. A new study, funded by the National Institutes of Health, leads researchers to believe that the accumulation occurs because of impaired clearance as opposed to an abnormally high production of the proteins.
Beta-Amyloid Protein Cleared 30 Percent More Slowly in those with Alzheimer's Disease
Senior author Randall Bateman MD, an assistant professor of neurology at Washington University in St. Louis, and colleagues measured beta amyloid levels in the cerebrospinal fluid of 12 patients who had late-onset Alzheimer’s disease and in 12 cognitively normal individuals. The average age of the study participants was 74.
Amyloid is a general term for protein fragments that the body produces normally. Beta-amyloid is a fragment snipped from an amyloid precursor protein (APP). In a healthy brain, these fragments are broken down and eliminated. In Alzheimer’s disease beta-amyloid protein fragments accumulate to form hard plaques between neurons, blocking the transmission of messages and leading to the death of brain cells and, ultimately, dementia.
The researchers used an innovative process they developed called stable isotope-linked kinetics or SILK. During the first nine hours, the patients received an intravenous drop of the amino acid leucine that had been labeled with a non-radioactive isotope. Cells in the brain pick up the labeled leucine and incorporate it into new copies they make of amyloid-beta and other proteins. CSF fluid was drawn every hour for 36 hours through a lumbar catheter.
By measuring the amount of beta-amyloid containing the labeled leucine, the researchers are able to calculate how fast the brain produces the protein and the rate in which it is cleared. While there was no indication that the brain of Alzheimer patients produced more beta-amyloid, the clearance of the protein fragments was about 30 percent slower in those with Alzheimer’s disease than in cognitively normal individuals.
"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
"Abnormal protein deposits within the brain are a hallmark not only of Alzheimer's disease, but of many neurological disorders. With knowledge about how these proteins accumulate, we may be able to slow that process and reduce the damage to the brain," said Roderick Corriveau, Ph.D., program director at NIH's National Institute of Neurological Disorders and Stroke (NINDS).
Alzheimer's disease is the most common cause of dementia in older adults, and affects as many as 5.3 million Americans. In the late-onset type of Alzheimer’s disease, symptoms usually appear after age 65.
Mawuenyega, KG et al. "Decreased clearance of amyloid-beta in the CNS of humans with Alzheimer’s disease." Science, published online December 9, 2010.