A ketone ester diet exhibits anxiolytic and cognition-sparing properties, and lessens amyloid and tau pathologies in a mouse model of Alzheimer%26apos;s disease

作者：Kashiwaya Yoshihiro; Bergman Christian; Lee Jong Hwan; Wan Ruiqian; King M Todd; Mughal Mohamed R; Okun Eitan; Clarke Kieran; Mattson Mark P^*; Veech Richard L

来源：Neurobiology of Aging, 2013, 34(6): 1530-1539.

DOI：10.1016/j.neurobiolaging.2012.11.023

• Cognitive deficits
• Hippocampus
• Amygdala
• 3xTgAD
• Frontotemporal lobe dementia
• Energy Metabolism
• Anxiety

Alzheimer%26apos;s disease (AD) involves progressive accumulation of amyloid beta-peptide (A beta) 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 esterebased 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 A beta 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. Published by Elsevier Inc.

• 出版日期2013-6