UBIQUITIN (UB) INTERACTS NONCOVALENTLY WITH ALZHEIMER AMYLOID PRECURSOR PROTEIN (BETA-PP) - ISOLATION OF UB-BETA-PP CONJUGATES FROM BRAIN EXTRACTS

UBIQUITIN (Ub)-immunocytochemistry on Alzheimer's disease (AD) brain s ections shows diverse Ub-associated deposits in the neuropil and senil e plaques, elevated levels of Ub reactivity in hippocampal neurons and glia, and co-localization of Ub and beta-amyloid precursor protein (b eta PP) epitope reactivity in dystrophic axons. These observations may suggest a role for Ub and stress-related mechanisms in AD pathogenesi s. Here we show for the first time that Ub interacts avidly but non-co valently beta PP and such complexes, apparently form in vivo, can be i solated from AD brain extracts by Ub-gel matrix affinity chromatograph y. Polyclonal antibodies specific to Ub and to different regions of be ta PP were employed to characterize these proteins. The implication of Ub-beta PP complex formation is discussed in the context of beta PP p rocessing.