Calorie restriction attenuates Alzheimer's disease type brain amyloidosis in Squirrel monkeys (Saimiri sciureus).
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.
Qin
Weiping
W
Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA.
Chachich
Mark
M
Lane
Mark
M
Roth
George
G
Bryant
Mark
M
de Cabo
Rafael
R
Ottinger
Mary Ann
MA
Mattison
Julie
J
Ingram
Donald
D
Gandy
Samuel
S
Pasinetti
Giulio Maria
GM
D000544:Alzheimer Disease / Q000473:pathology*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000686:Amyloidosis / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000473:pathology; D031204:Caloric Restriction; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012453:Saimiri; D056564:Sirtuin 1; D037761:Sirtuins / Q000378:metabolism; D054460:rho-Associated Kinases
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; C515851:ROCK1 protein, human; C515854:Rock1 protein, mouse; D054460:rho-Associated Kinases; D053829:Amyloid Precursor Protein Secretases; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D037761:Sirtuins