Recent studies from our laboratories and others suggest that calorie restriction (CR) may benefit Alzheimer's disease (AD) by preventing amyloid-β (Aβ) neuropathology in the mouse models of AD. Moreover, we found that promotion of the NAD + -dependent SIRT1 mediated deacetylase activity, a key regulator in CR extension of life span, may be a mechanism by which CR influences AD-type neuropathology. In this study we continued to explore the role of CR in AD-type brain amyloidosis in Squirrel monkeys (Saimiri sciureus). Monkeys were maintained on the normal and CR diets throughout the entire lifespan until they died of natural causes. We found that 30% CR resulted in reduced contents of Aβ1−40 and Aβ1−42 peptides in the temporal cortex of Squirrel monkeys, relative to control (CON) fed monkeys. The decreased contents of cortical Aβ peptide inversely correlated with SIRT1 protein concentrations in the same brain region; no detectable change in total full-length amyloid-β protein precursor (AβPP) level was found. Most interestingly, we found that 30% CR resulted in a select elevation of αbut not βor γsecretase activity which coincided with decreased ROCK1 protein content in the same brain region, relative to CON group. Collectively, the study suggests that investigation of the role of CR in non-human primates may provide a valuable approach for further clarifying the role of CR in AD.

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