Article

Calorie restriction attenuates Alzheimer's disease type brain amyloidosis in Squirrel monkeys (Saimiri sciureus)

Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA.
Journal of Alzheimer's disease: JAD (Impact Factor: 3.61). 01/2007; 10(4):417-22.
Source: PubMed

ABSTRACT Recent studies from our laboratories and others suggest that calorie restriction (CR) may benefit Alzheimer's disease (AD) by preventing amyloid-beta (Abeta) 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 Abeta1-40 and Abeta1-42 peptides in the temporal cortex of Squirrel monkeys, relative to control (CON) fed monkeys. The decreased contents of cortical Abeta peptide inversely correlated with SIRT1 protein concentrations in the same brain region; no detectable change in total full-length amyloid-beta protein precursor (AbetaPP) level was found. Most interestingly, we found that 30% CR resulted in a select elevation of alpha- but not beta- or gamma- secretase 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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    • "The protective effect of SIRT1 against AD was initially observed in CR studies, where CR reduced Aβ and plaque generation in the brains of transgenic AD mice (Patel et al., 2005; Wang et al., 2005a). Similarly, the reduction of Aβ was also noticed in the cortex of fasted squirrel monkeys and is inversely correlated with SIRT1 levels (Qin et al., 2006a). These studies imply that SIRT1 is involved in neuroprotection against AD. "
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    • "The protective effect of SIRT1 against AD was initially observed in caloric restriction studies, where calorie restriction reduced Aβ and plaque generation in the brains of transgenic AD mice (Patel et al., 2005; Wang et al., 2005a). Similarly, the reduction of Aβ is also noticed in the cortex of starved squirrel monkeys and is inversely correlated with SIRT1 levels (Qin et al., 2006a). These studies imply that SIRT1 is involved in the neuroprotection against AD. "
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    • "The authors further showed that SIRT1 can deacetylate and coactivate the retinoic acid receptor β, a known modulator of ADAM10 transcription (Donmez et al., 2010). Collectively, the original discovery from Qin et al. (2006a, 2006b) and the confirmatory studies from Donmez et al. (2010) suggest that pharmacological activation of SIRT1 may represent a promising approach to prevent amyloid deposition and neurodegeneration in AD (Wang et al., 2010a, 2010b). "
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