A? aggregation profiles and shifts in APP processing favor amyloidogenesis in canines.

ABSTRACT: The aged canine is a higher animal model that naturally accumulates ?-amyloid (A?) and shows age-related cognitive decline. However, profiles of A? accumulation in different species (40 vs. 42), its assembly states, and A? precursor protein (APP) processing as a function of age remain unexplored. In this study, we show that A? increases progressively with age as detected in extracellular plaques and biochemically extractable A?40 and A?42 species. Soluble oligomeric forms of the peptide, with specific increases in an A? oligomer migrating at 56 kDa, also increase with age. Changes in APP processing could potentially explain why A? accumulates, and we show age-related shifts toward decreased total APP protein and nonamyloidogenic (?-secretase) processing coupled with increased amyloidogenic (?-secretase) cleavage of APP. Importantly, we describe A? pathology in the cingulate and temporal cortex and provide a description of oligomeric A? across the canine lifespan. Our findings are in line with observations in the human brain, suggesting that canines are a valuable higher animal model for the study of A? pathogenesis.

SUBMITTER: Pop V 

PROVIDER: S-EPMC2932860 | biostudies-other | 2012 Jan

REPOSITORIES: biostudies-other