AMYLOID-BETA PROTEIN AND ITS 3-KDA FRAGMENT ARE PRESENT IN THE AXOPLASM FRACTION OF THE WHITE-MATTER IN HUMAN BRAIN

Production of the soluble amyloid beta-protein (A beta) precedes abnor mal accumulation of A beta amyloid in the brains of subjects with Alzh eimer's disease. To determine the cellular source and generating mecha nisms of soluble A beta in the human brain, we separated an axoplasm f raction from the cerebral white matter and analyzed it. The axoplasm f raction contained secretory isoforms of beta-amyloid precursor protein (APP) and 11.5 kDa A beta-bearing carboxyl-terminal fragments (CTFs) of APP. Furthermore, soluble 4 kDa A beta and 3 kDa fragments of A bet a (p3) were obtained from the axoplasm fraction. These results suggest that amyloidogenic 4 kDa A beta is intracellularly produced in cerebr al neurons and carried through the axons in human brain. (C) 1996 Acad emic Press, Inc.