title: Reduction of β-amyloid and γ-secretase by calorie restriction in female Tg2576 mice.
abstract: Research indicates that female risk of developing Alzheimer's disease (AD) is greater than that of males. Moderate reduction of calorie intake, known as calorie restriction (CR), reduces pathology in AD mouse models and is a potentially translatable prevention measure for individuals at-risk for AD, as well as an important tool for understanding how the brain endogenously attenuates age-related pathology. Whether sex influences the response to CR remains unknown. In this study, we assessed the effect of CR on beta-amyloid peptide (Aβ) pathology and hippocampal CA1 neuron specific gene expression in the Tg2576 mouse model of cerebral amyloidosis. Relative to ad libitum (AL) feeding, CR feeding significantly reduced hippocampal Aβ burden in 15-month-old female, but not age-matched male, Tg2576 mice. Sustained CR also significantly reduced expression of presenilin enhancer 2 (Psenen) and presenilin 1, components of the γ-secretase complex, in Tg2576 females. These results indicate that long-term CR significantly reduces age-dependent female Tg2576 Aβ pathology, which is likely to involve CR-mediated reductions in γ-secretase-dependent amyloid precursor protein (APP) metabolism.
authors.affiliation: Cell and Molecular Biology Program, New York University Langone Medical Center, New York, NY, USA; Department of Cell Biology, New York University Langone Medical Center, New York, NY, USA; Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY, USA.
authors.forename: Marissa J
authors.initials: MJ
authors.lastname: Schafer
authors.affiliation: Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY, USA; Department of Psychiatry, New York University Langone Medical Center, New York, NY, USA.
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Alldred
authors.affiliation: Division of Medical Physics, Nathan Kline Institute, Orangeburg, NY, USA.
authors.forename: Sang Han
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Sinq Systems, Silver Spring, MD, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Calhoun
authors.affiliation: Department of Child and Adolescent Psychiatry, New York University Langone Medical Center, New York, NY, USA; Division of Child Psychiatry, Nathan Kline Institute, Orangeburg, NY, USA.
authors.forename: Eva
authors.initials: E
authors.lastname: Petkova
authors.affiliation: Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY, USA; Department of Psychiatry, New York University Langone Medical Center, New York, NY, USA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Mathews
authors.affiliation: Cell and Molecular Biology Program, New York University Langone Medical Center, New York, NY, USA; Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY, USA; Department of Psychiatry, New York University Langone Medical Center, New York, NY, USA; Department of Physiology & Neuroscience, New York University Langone Medical Center, New York, NY, USA. Electronic address: ginsberg@nki.rfmh.org.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Ginsberg
mesh_terms: D000375:Aging / Q000235:genetics; D000544:Alzheimer Disease / Q000209:etiology* / Q000517:prevention & control*; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism; D031204:Caloric Restriction; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D008822:Mice, Transgenic; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism; D012306:Risk; D012737:Sex Factors
chemical_list: D016229:Amyloid beta-Peptides; D053764:Presenilin-1; C580804:presenilin 1, mouse; D053829:Amyloid Precursor Protein Secretases; C555827:presenilin enhancer 2, mouse
keywords: Abeta; Aging; Alzheimer's disease; Amyloid-beta precursor protein; CA1 pyramidal neurons; Calorie restriction; Entorhinal cortex; Hippocampus; Microarray; Mouse model; qPCR