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 A beta is a normal metabolic product and is present in cerebrospinal fluid. We identified soluble A beta 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 residue 40. Analysis of cerebrospinal fluid from the same subjects confirmed the presence of only 4kD A beta in comparable amounts in AD and controls. The presence of soluble A beta only in brain regions with amyloid suggests they are related. The undetectability of soluble A beta in control brains indicates that it is normally removed or bound to other proteins. Failure of this protective mechanism might cause amyloid formation in AD.