title: High-Fat-Diet Intake Enhances Cerebral Amyloid Angiopathy and Cognitive Impairment in a Mouse Model of Alzheimer's Disease, Independently of Metabolic Disorders.
abstract: The high-fat Western diet is postulated to be associated with the onset and progression of Alzheimer's disease (AD). However, the role of high-fat-diet consumption in AD pathology is unknown. This study was undertaken to examine the role of high-fat-diet intake in AD.
  
  
  
  5XFAD mice, a useful mouse model of AD, and control wild-type mice were fed (1) high-fat diet or (2) control diet for 10 weeks. The effects on cerebral AD pathology, cognitive function, and metabolic parameters were compared between each group of mice. High-fat diet significantly enhanced cerebrovascular β-amyloid (Aβ) deposition (P<0.05) and impaired cognitive function (P<0.05) in 5XFAD mice, but not in wild-type mice. High-fat diet enhanced hippocampal oxidative stress (P<0.05) and NADPH oxidase subunits, gp91(phox) (P<0.01) and p22(phox) (P<0.01) in 5XFAD mice, but not in wild-type mice. Furthermore, high-fat diet reduced cerebral occludin (P<0.05) in 5XFAD mice, but not in wild-type mice. Thus, 5XFAD mice exhibited greater susceptibility to high-fat diet than wild-type mice regarding cerebrovascular injury and cognitive impairment. On the other hand, 5XFAD mice fed high-fat diet exhibited much less increase in body weight, white adipose tissue weight, and adipocyte size than their wild-type counterparts. High-fat diet significantly impaired glucose tolerance in wild-type mice but not in 5XFAD mice. Thus, 5XFAD mice had much less susceptibility to high-fat-diet-induced metabolic disorders than wild-type mice.
  
  
  
  High-fat diet, independently of metabolic disorders, significantly promotes the progression of AD-like pathology through enhancement of cerebral amyloid angiopathy and oxidative stress.
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Chuo-ku, Kumamoto, Japan Department of Urology, Heilongjiang Provincial Hospital, Harbin, Heilongjiang, China.
authors.forename: Bowen
authors.initials: B
authors.lastname: Lin
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Chuo-ku, Kumamoto, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Hasegawa
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Chuo-ku, Kumamoto, Japan Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Nishi-shinbashi, Minato-ku, Tokyo, Japan.
authors.forename: Koki
authors.initials: K
authors.lastname: Takane
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Chuo-ku, Kumamoto, Japan.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Koibuchi
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Chuo-ku, Kumamoto, Japan.
authors.forename: Cheng
authors.initials: C
authors.lastname: Cao
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Chuo-ku, Kumamoto, Japan mitsuyam@gpo.kumamoto-u.ac.jp.
authors.forename: Shokei
authors.initials: S
authors.lastname: Kim-Mitsuyama
mesh_terms: D000273:Adipose Tissue / Q000473:pathology; D000544:Alzheimer Disease / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D000682:Amyloid / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D001921:Brain / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D016657:Cerebral Amyloid Angiopathy / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D002561:Cerebrovascular Disorders / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D060825:Cognitive Dysfunction / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D004326:Drinking / Q000502:physiology; D004435:Eating / Q000502:physiology; D005951:Glucose Tolerance Test; D008297:Male; D018782:Maze Learning; D008815:Mice, Inbred Strains; D019255:NADPH Oxidases / Q000378:metabolism; D062793:Occludin / Q000378:metabolism; D009929:Organ Size / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D013482:Superoxide Dismutase / Q000378:metabolism; D014556:Urine / Q000502:physiology
chemical_list: D000682:Amyloid; D001786:Blood Glucose; D019208:Brain-Derived Neurotrophic Factor; D062793:Occludin; D002374:Catalase; D051546:Cyclooxygenase 2; D013482:Superoxide Dismutase; D019255:NADPH Oxidases
keywords: brain; cerebrovascular disorders; nutrition; obesity