title: Calorie restriction attenuates Alzheimer's disease type brain amyloidosis in Squirrel monkeys (Saimiri sciureus).
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.
authors.affiliation: Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Weiping
authors.initials: W
authors.lastname: Qin
authors.forename: Mark
authors.initials: M
authors.lastname: Chachich
authors.forename: Mark
authors.initials: M
authors.lastname: Lane
authors.forename: George
authors.initials: G
authors.lastname: Roth
authors.forename: Mark
authors.initials: M
authors.lastname: Bryant
authors.forename: Rafael
authors.initials: R
authors.lastname: de Cabo
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Ottinger
authors.forename: Julie
authors.initials: J
authors.lastname: Mattison
authors.forename: Donald
authors.initials: D
authors.lastname: Ingram
authors.forename: Samuel
authors.initials: S
authors.lastname: Gandy
authors.forename: Giulio Maria
authors.initials: GM
authors.lastname: Pasinetti
mesh_terms: 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
chemical_list: 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