title: Increased Aβ pathology in aged Tg2576 mice born to mothers fed a high fat diet.
abstract: Maternal obesity is associated with increased risk of developing diabetes, obesity and premature death in adult offspring. Mid-life diabetes, hypertension and hypercholesterolaemia are risk factors for the development of sporadic Alzheimer's disease (AD). A key pathogenic feature of AD is the accumulation of β-amyloid (Aβ) in the brain. The purpose of this study was to investigate the effect of high fat diet feeding during early life on Aβ pathology in the Tg2576 mouse model of AD. Female mice were fed a standard (C) or high fat (HF) diet before mating and during gestation and lactation. At weaning, male offspring were fed a C diet. Significantly higher levels of guanidine-soluble Aβ and plaque loads were observed in the hippocampi of 11-month old Tg2576 mice born to mothers fed a HF diet. Changes in the extracellular matrix led to increased retention of Aβ within the parenchyma. These data support a role for maternal and gestational health on the health of the aged brain and pathologies associated with AD and may provide a novel target for both the prevention and treatment of AD.
authors.affiliation: Dept. of Life, Health and Chemical Sciences, Faculty of Science, Open University, Walton Hall, Milton Keynes, UK.
authors.forename: Shereen
authors.initials: S
authors.lastname: Nizari
authors.affiliation: Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
authors.forename: Roxana O
authors.initials: RO
authors.lastname: Carare
authors.affiliation: Dept. of Life, Health and Chemical Sciences, Faculty of Science, Open University, Walton Hall, Milton Keynes, UK.
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Hawkes
mesh_terms: D000375:Aging; D000544:Alzheimer Disease / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D051379:Mice; D008822:Mice, Transgenic; D058225:Plaque, Amyloid; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers