title: A ketone ester diet exhibits anxiolytic and cognition-sparing properties, and lessens amyloid and tau pathologies in a mouse model of Alzheimer's disease.
abstract: Alzheimer's disease (AD) involves progressive accumulation of amyloid β-peptide (Aβ) and neurofibrillary pathologies, and glucose hypometabolism in brain regions critical for memory. The 3xTgAD mouse model was used to test the hypothesis that a ketone ester-based diet can ameliorate AD pathogenesis. Beginning at a presymptomatic age, 2 groups of male 3xTgAD mice were fed a diet containing a physiological enantiomeric precursor of ketone bodies (KET) or an isocaloric carbohydrate diet. The results of behavioral tests performed at 4 and 7 months after diet initiation revealed that KET-fed mice exhibited significantly less anxiety in 2 different tests. 3xTgAD mice on the KET diet also exhibited significant, albeit relatively subtle, improvements in performance on learning and memory tests. Immunohistochemical analyses revealed that KET-fed mice exhibited decreased Aβ deposition in the subiculum, CA1 and CA3 regions of the hippocampus, and the amygdala. KET-fed mice exhibited reduced levels of hyperphosphorylated tau deposition in the same regions of the hippocampus, amygdala, and cortex. Thus, a novel ketone ester can ameliorate proteopathic and behavioral deficits in a mouse AD model.
authors.affiliation: Laboratory of Metabolic Control, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kashiwaya
authors.forename: Christian
authors.initials: C
authors.lastname: Bergman
authors.forename: Jong-Hwan
authors.initials: JH
authors.lastname: Lee
authors.forename: Ruiqian
authors.initials: R
authors.lastname: Wan
authors.forename: M Todd
authors.initials: MT
authors.lastname: King
authors.forename: Mohamed R
authors.initials: MR
authors.lastname: Mughal
authors.forename: Eitan
authors.initials: E
authors.lastname: Okun
authors.forename: Kieran
authors.initials: K
authors.lastname: Clarke
authors.forename: Mark P
authors.initials: MP
authors.lastname: Mattson
authors.forename: Richard L
authors.initials: RL
authors.lastname: Veech
mesh_terms: D000544:Alzheimer Disease / Q000178:diet therapy / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000009:adverse effects / Q000378:metabolism*; D000818:Animals; D001007:Anxiety / Q000178:diet therapy / Q000378:metabolism* / Q000473:pathology; D003072:Cognition Disorders / Q000178:diet therapy / Q000378:metabolism* / Q000473:pathology; D055423:Diet, Ketogenic / Q000379:methods*; D004195:Disease Models, Animal; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011897:Random Allocation; D016875:tau Proteins / Q000009:adverse effects / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; C558298:Mapt protein, mouse; D016875:tau Proteins