# Dietary restriction and associated changes in gut microbiota to prevent Alzheimer disease

> **NIH NIH R21** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2020 · $186,875

## Abstract

PROJECT SUMMARY/ABSTRACT
Our hypothesis is that overnutrition coupled with impaired dietary amino acid turnover may play a role in
Alzheimer disease (AD) pathogenesis. goals are to manage amyloid and tangle homeostasis by nutrition to
prevent and treat AD. Restriction of protein, Leu, Met, branched-chain amino acids (BCAA) can improve
longevity in rodents without calorie restriction. Failure of Met or BCAA degradation are caused by inherited
diseases -- homocystinuria and maple syrup urine disease -- that are fatal when untreated and cause mental
retardation. Treatments include restricting Met or BCAA or Leu. Therefore, our hypothesis is that MR and BCAA-
R can help in managing and preventing AD by limiting metabolic load and epigenetic changes. The primary
purpose of this study is to treat amyloidosis and tauopathy in an AD mouse model by restricting Met levels and
to compare the treatments with other dietary restriction (DR) approaches. We propose that by restricting Met
and other nutrients, the reduced metabolic load will lead to a fasting condition and reduce amyloid β (Aβ) protein
precursor (APP) levels due to its rapid turnover (20 min half-life).
 The studies will use behavior as an endpoint to measure overall health of the mice. Although behavior is
a complex change that may not linearly correlate with degeneration and pathology, it provides a go/no go
decision for mental health improvement.
 We will use tissues from control and restricted mice to follow AD-like neuropathology and neuronal
integrity to test the hypothesis that the interventions can prevent AD and related dementias. Most studies on AD
have focused on Aβ and senile plaques. A salient feature of the current study is that we will determine the effects
of DR on Aβ, Microtubule-associated protein Tau (MAPT) and a combination of both lesions in littermates.
 Finally, it has recently been recognized that the number of microbes rival human cells particularly in the
alimentary canal. Moreover, studies have shown that the gut microbiota can affect nutrition, and vice versa, in
both positive and negative ways and impact immune, metabolic and neurological functions. Hence, it is important
to understand the associations between gut microbiota composition, dietary modification and disease outcome
to realize the contribution of gut microbes to dietary intervention of AD associated neuropathology. We will
therefore examine the gut microbiome in all the treatments.
 Since a 1.5 x increase in APP can induce FAD, the small reduction over time in its expression should
prevent or delay AD. Dietary restriction and exercise may provide useful paradigms that may be readily
implemented for prevention of AD.

## Key facts

- **NIH application ID:** 9905467
- **Project number:** 5R21AG062378-02
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** KUMAR SAMBAMURTI
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $186,875
- **Award type:** 5
- **Project period:** 2019-04-15 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9905467

## Citation

> US National Institutes of Health, RePORTER application 9905467, Dietary restriction and associated changes in gut microbiota to prevent Alzheimer disease (5R21AG062378-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9905467. Licensed CC0.

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