# Brain Glycogen - Metabolism, Mechanisms, and Therapeutic Potential

> **NIH NIH R35** · UNIVERSITY OF KENTUCKY · 2021 · $382,500

## Abstract

This is an Administrative Supplement request in response to NOT-NS-21-040 for “Collaborative Activities to
Promote Sleep/Circadian Research in ADRD” for R35NS116824 entitled “Brain Glycogen – Metabolism,
Mechanisms, and Therapeutic Potential.” The requested funds are to perform metabolomics, histology, and
RNA-sequencing experiments proposed within the scope of R35NS116824 on Alzheimer's disease mouse
models with the addition of including sleep disruption to the methods. The parent grant focuses on defining
how aberrant intracellular glycogen-like aggregates, known as polyglucosan bodies (PGBs), impact
neurodegeneration. The work is centered on both Alzheimer's disease and the childhood dementia Lafora
disease with efforts to define how perturbations in metabolism impact disease progression and test a pre-
clinical therapeutic option to ablate PGBs and test the biological outcome. We hypothesize that sleep
fragmentation will increase PGB formations and our preliminary data strongly suggests that increased PGBs
will negatively impact brain metabolism. A significant strength of this supplement is that it brings together two
principle investigators that have non-overlapping and complementary expertise and who have not collaborated
together in the past. The supplement will also utilize the wealth of expertise and resources provided by the UK
Alzheimer's Disease Center (ADC). In this supplement, we will utilize our extensive expertise with PGBs to:
Aim 1: Define PGBs, metabolic profiles, gene expression, and AD hallmarks during disrupted sleep.
Aim 2: Assess AD hallmarks during disrupted sleep in AD animals treated with VAL-0417.

## Key facts

- **NIH application ID:** 10401225
- **Project number:** 3R35NS116824-02S2
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Matthew S. Gentry
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $382,500
- **Award type:** 3
- **Project period:** 2020-05-15 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10401225

## Citation

> US National Institutes of Health, RePORTER application 10401225, Brain Glycogen - Metabolism, Mechanisms, and Therapeutic Potential (3R35NS116824-02S2). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10401225. Licensed CC0.

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