Amyloid β Protein and Its 3-kDa Fragment Are Present in the Axoplasm Fraction of the White Matter in Human Brain

Abstract

Production of the soluble amyloid β-protein (Aβ) precedes abnormal accumulation of Aβ amyloid in the brains of subjects with Alzheimer's disease. To determine the cellular source and generating mechanisms of soluble Aβ in the human brain, we separated an axoplasm fraction from the cerebral white matter and analyzed it. The axoplasm fraction contained secretory isoforms of β-amyloid precursor protein (APP) and 11.5 kDa Aβ-bearing carboxyl-terminal fragments (CTFs) of APP. Furthermore, soluble 4 kDa Aβ and 3 kDa fragments of Aβ (p3) were obtained from the axoplasm fraction. These results suggest that amyloidogenic 4 kDa Aβ is intracellularly produced in cerebral neurons and carried through the axons in human brain.