SOLUBLE AMYLOID BETA-PROTEIN IS A MARKER OF ALZHEIMER AMYLOID IN BRAIN BUT NOT IN CEREBROSPINAL-FLUID

The amyloid beta protein (A beta), a 4 kD fragment of the beta amyloid precursor protein, is deposited as insoluble amyloid in the brain of Alzheimer disease (AD) subjects. Soluble go is a normal metabolic prod uct and is present in cerebrospinal fluid. We identified soluble A bet a forms of 4kD, 3kD and 3.7kD in AD but not in control brains free of amyloid deposits. All three forms of soluble A beta extend beyond resi due 40. Analysis of cerebrospinal fluid from the same subjects confirm ed the presence of only 4kD A beta in comparable amounts in AD and con trols. The presence of soluble A beta only in brain regions with amylo id suggests they are related. The undetectability of soluble go in con trol brains indicates that it is normally removed or bound to other pr oteins. Failure of this protective mechanism might cause amyloid forma tion in AD. (C) 1994 Academic Press, Inc.