Ubiquitin (Ub) interacts non-covalently with Alzheimer amyloid precursor protein (betaPP): isolation of Ub-betaPP...

Ubiquitin (Ub)-immunocytochemistry on Alzheimer's disease (AD) brain sections shows diverse Ub-associated deposits in the neuropil and senile plaques, elevated levels of Ub reactivity in hippocampal neurons and glia, and co-localization of Ub and beta-amyloid precursor protein (betaPP) epitope reactivity in dystrophic axons. These observations may suggest a role for Ub and stress-related mechanisms in AD pathogenesis. Here we show for the first time that Ub interacts avidly but non-covalently with betaPP and such complexes, apparently formed in vivo, can be isolated from AD brain extracts by Ub-gel matrix affinity chromatography. Polyclonal antibodies specific to Ub and to different regions of betaPP were employed to characterize these proteins. The implication of Ub-betaPP complex formation is discussed in the context of betaPP processing.