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.
Original language | English |
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Pages (from-to) | 1530-1539 |
Number of pages | 10 |
Journal | Neurobiology of Aging |
Volume | 34 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2013 |
Bibliographical note
Funding Information:The authors thank Andrew Holmes, Elizabeth Gratton, and Shireesh Srivastava for scientific advice and technical assistance. This research was supported by the Intramural Research Programs of the National Institute on Aging and the National Institute on Alcohol Abuse and Alcoholism .
Funding
The authors thank Andrew Holmes, Elizabeth Gratton, and Shireesh Srivastava for scientific advice and technical assistance. This research was supported by the Intramural Research Programs of the National Institute on Aging and the National Institute on Alcohol Abuse and Alcoholism .
Funders | Funder number |
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National Institute on Alcohol Abuse and Alcoholism | |
National Institute on Aging | ZIAAG000317 |
Keywords
- 3xTgAD
- Amygdala
- Anxiety
- Cognitive deficits
- Energy Metabolism
- Frontotemporal lobe dementia
- Hippocampus