# Ketogenic diet approaches to slow disease progression in a rat model of Alzheimer's disease

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $431,750

## Abstract

Project Summary
Alzheimer’s disease is the most common age-related neurodegenerative disease, and there is a clear need to
develop effective approaches to treat or prevent the cognitive impairment that is the prominent symptom of this
disease. Neuroinflammation and mitochondrial impairments have been implicated in the pathogenesis of
Alzheimer’s disease, and ketogenic diets have been reported to decrease inflammation and enhance
mitochondrial function. This has led to speculation that ketogenic diets may provide an effective approach to
treat Alzheimer’s disease. In support of this idea, short-term (≤3 months) studies have shown that ketogenic
diets improve motor function in mouse models of Alzheimer’s disease. However, memory was not improved
with this diet, perhaps because the impact of the ketogenic diet was blunted by the ad libitum feeding approach
used in these studies. There is growing appreciation that physiological response to a high fat diet is likely
dependent on level of energy intake. Ketogenic diets are inherently high in fat and ad libitum feeding of a high
fat diet induces a metabolic stress that may impair cognitive function. To investigate the physiological impact
of these diets independent of differences in energy intake, we fed mice a ketogenic diet in isocaloric amounts
to a control diet and found that the ketogenic diet increased life span and preserved memory and motor
function with advanced age. It remains to be determined whether this feeding approach, which produces
sustained ketosis, would also improve memory in rodent models of Alzheimer’s disease. Calorie restriction
and intermittent fasting, which produce intermittent periods of ketosis, have also been reported to mitigate
cognitive impairments in mouse models of Alzheimer’s disease. This raises the possibility that ketosis does
not need to be continuous to have a beneficial impact on memory, which if true, would provide a lifestyle
change more likely to be adopted by at-risk individuals. Sustained or intermittent increases in blood ketone
levels with consumption of a ketogenic diet may be particularly beneficial if they lessen inflammation. Thus, we
hypothesize that isocaloric ketogenic diet feeding approaches that produce either sustained or intermittent
ketosis will decrease neuroinflammation and delay the onset or lessen the severity of disease progression in
the TgF344-AD rat model of Alzheimer’s disease. We propose two specific aims to test this hypothesis: 1)
determine if an isocaloric ketogenic diet feeding approach slows disease progression in the TgF344-AD rat; 2)
determine if intermittent feeding of a ketogenic diet is sufficient to delay the onset or lessen the severity of
memory and motor deficits in the TgF344-AD rat. These studies will take an important step toward determining
if ketogenic diet approaches provide a viable strategy to treat or prevent Alzheimer’s disease.

## Key facts

- **NIH application ID:** 9977496
- **Project number:** 1R21AG064290-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Pamela J Lein
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $431,750
- **Award type:** 1
- **Project period:** 2020-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9977496

## Citation

> US National Institutes of Health, RePORTER application 9977496, Ketogenic diet approaches to slow disease progression in a rat model of Alzheimer's disease (1R21AG064290-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9977496. Licensed CC0.

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