MODIFIED AMYLOID-BETA PROTEIN ENDING AT 42 OR 40 WITH DIFFERENT SOLUBILITY ACCUMULATES IN THE BRAIN OF ALZHEIMERS-DISEASE

Serial extraction study of Alzheimer's disease (AD) and control brains revealed 4, 3.7 and 3 kD amyloid beta protein (A beta) species accumulated in AD brains. In the fractions extracted with TBS, 10% SDS and formic acid, considerable amounts of A beta species were recovered in SDS fractions besides TBS and formic acid tractions. Immunoblotting with several site-specific antibodies confirmed not only the presence of 4 kD A beta starting at the first amino acid of A beta but also 2 smaller A beta species with modification of their amino-termini in the highly resolutional Tris/Tricine gel system. A beta solubility using these solvents was associated with both modification of the amino-terminus and length of carboxyl-terminus of A beta. Especially, a large amount of modified A beta was found to be accumulated as forms with different solubility in AD brains. (C) 1995 Academic Press, Inc.