Fractionation of amyloid beta-protein (A beta) in Alzheimer's disease and Down's syndrome brains. Presence of membrane-bound A beta.
To investigate the early stage of beta-amyloidogenesis in Alzheimer's disease (AD), we performed sucrose density gradient fractionation of amyloid beta-protein (A beta) deposited in cerebral cortices from AD and Down's syndrome patients and normal aged individuals. Each fraction was subjected to Western blotting with monoclonal antibodies BA27 and BC05, which specifically recognize A beta 40 and A beta 42, respectively. The samples from brains with a large number of diffuse plaques showed strong BC05 immunoreactivity at the 1.0/1.2 M (F1) and 1.2/1.5 M (F2) interfaces. In contrast, in brains with advanced AD pathology, most of the BC05 immunoreactivity was recovered at the 1.5/2.0 M (F3) interface. In all cases, the level of BA27 immunoreactivity was negligible. Although F1A beta was determined to be A beta 1-42, it was only weakly reactive with BAN50 (monoclonal antibody raised against A beta 1-16). Delipidation of F1A beta restored full BAN50 immunoreactivity, indicating that F1A beta is bound to membrane. The present results suggest that diffuse plaques are associated with this membrane-bound A beta and thus that this novel A beta species is an initially deposited one.
Yanagisawa
K
K
Department of Neuropathology, Faculty of Medicine, University of Tokyo, Japan.
Asami-Odaka
A
A
Suzuki
N
N
Ihara
Y
Y
D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism*; D004314:Down Syndrome / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D013395:Sucrose / Q000494:pharmacology
D016564:Amyloid beta-Protein Precursor; D000911:Antibodies, Monoclonal; D013395:Sucrose