Kashiwaya · Neurobiology of aging 2013 · Controlled animal feeding study · n=?

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

Cited 366 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Animal research (preclinical mouse model)

PubMed 23276384 · doi:10.1016/j.neurobiolaging.2012.11.023 · record verified 2026-08-30

What was done

Male 3xTgAD mice were started at a presymptomatic age on either a diet containing a ketone ester precursor of ketone bodies (KET) or an isocaloric carbohydrate control diet. Behavioral assessments evaluating anxiety, learning, and memory were conducted at 4 and 7 months after diet initiation. Following behavioral testing, brain tissue was evaluated using immunohistochemistry to measure amyloid-β (Aβ) and hyperphosphorylated tau deposition across multiple brain regions, including the hippocampus (subiculum, CA1, CA3), amygdala, and cortex.

What was found

The abstract reports no specific numerical values, percentages, or confidence intervals. KET-fed mice showed statistically significant reductions in anxiety across two behavioral tests and significant, though subtle, improvements in learning and memory tests compared to controls. Immunohistochemical analysis demonstrated decreased Aβ deposition in the subiculum, CA1, CA3, and amygdala, alongside reduced hyperphosphorylated tau deposition in the same hippocampal subregions, amygdala, and cerebral cortex.

Why it matters

This study provides preclinical evidence that nutritional ketosis induced by an exogenous ketone ester can simultaneously reduce both amyloid and tau proteopathies while conferring behavioral and cognitive benefits in a standard transgenic Alzheimer's model.

Limits

Findings are restricted to a single transgenic mouse model (3xTgAD) and may not translate to human pathophysiology or clinical disease progression. The study tested only male mice, the abstract omits sample sizes and exact quantitative metrics, and no wild-type control arm is described in the abstract.

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