Linking cognition to age and amyloid-β burden in the brain of a nonhuman primate (Microcebus murinus)

Abstract

The gray mouse lemur (Microcebus murinus) is a valuable model in research on age-related proteopathies. This nonhuman primate, comparable to humans, naturally develops tau and amyloid-β proteopathies during aging. Whether these are linked to cognitive alterations is unknown. Here, standardized cognitive testing in pairwise discrimination and reversal learning in a sample of 37 aged (>5 years) subjects was combined with tau and amyloid-β histochemistry in individuals that died naturally. Correlation analyses in successfully tested subjects (n = 22) revealed a significant relation between object discrimination learning and age, strongly influenced by outliers, suggesting pathological cases. Where neuroimmunohistochemistry was possible, as subjects deceased, the naturally developed cortical amyloid-β burden was significantly linked to pretraining success (intraneuronal accumulations) and discrimination learning (extracellular deposits), showing that cognitive (pairwise discrimination) performance in old age predicts the natural accumulation of amyloid-β at death. This is the first description of a direct relation between the cortical amyloid-β burden and cognition in a nonhuman primate.