Soluble Amyloid β-Protein Is a Marker of Alzheimer Amyloid in Brain But Not in Cerebrospinal Fluid

The amyloid β protein (Aβ), a 4 kD fragment of the β amyloid precursor protein, is deposited as insoluble amyloid in the brain of Alzheimer disease (AD) subjects. Soluble Aβ is a normal metabolic product and is present in cerebrospinal fluid. We identified soluble Aβ forms of 4kD, 3kD and 3.7kD in AD but not in control brains free of amyloid deposits. All three forms of soluble Aβ extend beyond residue 40. Analysis of cerebrospinal fluid from the same subjects confirmed the presence of only 4kD Aβ in comparable amounts in AD and controls. The presence of soluble Aβ only in brain regions with amyloid suggests they are related. The undetectability of soluble Aβ 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.