21 March 2002. Predicting who may get Alzheimer's disease still is an almost impossible exercise. Yet with several promising treatments looming on the horizon, early diagnosis is becoming increasingly desirable. One clear indicator of trouble ahead is the deposition of amyloid-β (Aβ) in the brain, which precedes cognitive impairment by many years. The question is, how does one quantitate plaque formation in the brain of a living patient? The answer may be-you don't. Instead, examine their blood.
Reporting in tomorrow's Science, David Holtzman and colleagues at Washington University, St. Louis, Missouri, and Eli Lilly and Co., Indianapolis, show that the movement of Aβ to the plasma is a good indicator of the amount of the insoluble peptide in the brain. The researchers used transgenic mice that express high levels of mutated human amyloid precursor protein, and typically develop amyloid deposits at three to six months of age. When Ron DeMattos et al. inject these mice with an Aβ antibody, it begins to draw Aβ from the brain into the plasma (see related ARF news item). The scientists found that this efflux of Aβ from the brain directly correlates with the amount deposited there.
"The findings are interesting, but there may be some pitfalls in extrapolating [the technique] to humans," said Doug Galasko, University of California at San Diego. "There is a marked concentration gradient from the brain to the blood in the transgenic mice. In humans, there is a lesser concentration gradient, and an antibody might produce a less dramatic rise in plasma Aβ." It may also be more of a challenge to find people with relatively small elevations in brain Aβ levels.-Tom Fagan.
DeMattos RB, Bales KR, Cummins DJ, Paul SM, Holtzman DM. Brain to plasma amyloid-β efflux: a measure of brain amyloid burden in a mouse model of Alzheimer's disease. Science 2002 March 22;(295):2264-2267. Abstract