title: Perinatal Choline Supplementation Reduces Amyloidosis and Increases Choline Acetyltransferase Expression in the Hippocampus of the APPswePS1dE9 Alzheimer's Disease Model Mice.
abstract: Prevention of Alzheimer's disease (AD) is a major goal of biomedical sciences. In previous studies we showed that high intake of the essential nutrient, choline, during gestation prevented age-related memory decline in a rat model. In this study we investigated the effects of a similar treatment on AD-related phenotypes in a mouse model of AD. We crossed wild type (WT) female mice with hemizygous APPswe/PS1dE9 (APP.PS1) AD model male mice and maintained the pregnant and lactating dams on a control AIN76A diet containing 1.1 g/kg of choline or a choline-supplemented (5 g/kg) diet. After weaning all offspring consumed the control diet. As compared to APP.PS1 mice reared on the control diet, the hippocampus of the perinatally choline-supplemented APP.PS1 mice exhibited: 1) altered levels of amyloid precursor protein (APP) metabolites-specifically elevated amounts of β-C-terminal fragment (β-CTF) and reduced levels of solubilized amyloid Aβ40 and Aβ42 peptides; 2) reduced number and total area of amyloid plaques; 3) preserved levels of choline acetyltransferase protein (CHAT) and insulin-like growth factor II (IGF2) and 4) absence of astrogliosis. The data suggest that dietary supplementation of choline during fetal development and early postnatal life may constitute a preventive strategy for AD.
authors.affiliation: Department of Pathology & Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Tiffany J
authors.initials: TJ
authors.lastname: Mellott
authors.affiliation: Department of Pathology & Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Olivia M
authors.initials: OM
authors.lastname: Huleatt
authors.affiliation: Department of Pathology & Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Bethany N
authors.initials: BN
authors.lastname: Shade
authors.affiliation: Department of Pathology & Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Pender
authors.affiliation: Department of Pathology & Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Yi B
authors.initials: YB
authors.lastname: Liu
authors.affiliation: Department of Pathology & Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Slack
authors.affiliation: Department of Pathology & Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Jan K
authors.initials: JK
authors.lastname: Blusztajn
mesh_terms: D000544:Alzheimer Disease / Q000178:diet therapy / Q000235:genetics* / Q000517:prevention & control*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D000686:Amyloidosis / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D000831:Animals, Newborn; D002794:Choline / Q000008:administration & dosage*; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects; D011247:Pregnancy; D053764:Presenilin-1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D050505:Mutant Proteins; D053764:Presenilin-1; C580804:presenilin 1, mouse; D002795:Choline O-Acetyltransferase; D002794:Choline