Researchers seeking to identify Alzheimer's risk make significant progress by focusing on a specific blood biomarker
A simple blood test to detect whether a person might
develop Alzheimer's disease is within sight and could eventually help scientists
in their quest toward reversing the disease's onset in those likely to develop
the debilitating neurological condition. Building on a study that started 20 years
ago with an elderly population in Northern Manhattan at risk or in various stages
of developing Alzheimer's disease a Columbia University Medical Center research
group has yielded ground-breaking findings that could change the way the disease
is treated or someday prevent it.
Results presented online in the Proceedings of the National
Academy of Sciences during the week of Sept. 8, 2008 suggest that individuals
with elevated levels of a certain peptide in the blood plasma, Amyloid Beta 42
(As42), are at increased risk of developing Alzheimer's disease and that the decline
of As42 in the bloodstream may reflect the compartmentalization or "traffic jam"
of As42 in the brain, which occurs in the brain's of people with Alzheimer's.
"To date, As42 levels have measured most reliably in
the cerebrospinal fluid, which is more difficult to collect than blood," said
Nicole Schupf, Ph.D., Dr.P.H., associate professor of clinical epidemiology at
Columbia University Medical Center and lead author of the paper. "Blood draws
can be done with relative ease and greater frequency than spinal taps, which is
typically the way cerebrospinal fluid is collected."
In this study, researchers found that plasma levels of
As42 appear to increase before the onset of Alzheimer's disease and decline shortly
after the onset of dementia. Researchers surmise that As42 may become trapped
in the brain, which could account for the decrease in levels post-dementia.
The principal investigator on the Northern Manhattan
study, Richard Mayeux, M.D., M.S., professor of neurology, psychiatry, and epidemiology,
and co-director of the Taub Institute of Research on Alzheimer's Disease and the
Aging Brain at CUMC, likens the finding to something similar that is seen in patients
who have a heart attack, who typically have elevated lipid levels in their bloodstream
prior to a myocardial infarction (MI), but post-MI lipid levels may decrease.
Using more specific antibodies developed by the Ravetch
Laboratory at Rockefeller University, the researchers were able to hone in on
the most detrimental form of amyloid compound, the protofibrillar form of As,
according to Dr. Mayeux, who is the senior author of this paper.
While the cognitive impairments of Alzheimer's can be
monitored throughout the disease course, clinicians have had no reliable way to
monitor the pathologic progression of the disease. Being able to reliably measure
As levels in the blood could provide clinicians with a tool that forecasts the
onset of Alzheimer's much earlier. Earlier detection would of course be an important
step in combating the disease, researchers said.
This research is supported by a Program Project Grant
by the National Institutes' of Health National Institute of Aging. Other authors
on the paper from Columbia University Medical Center include Ming X. Tang, Ph.D.,
Jennifer Manly, Ph.D., and Howard Andrews, Ph.D. The Department of Immunology
at the New York State Institute for Basic Research in Developmental Disabilities,
Staten Island, New York, also contributed to this research.
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