# Inflammasome-based Alzheimer's disease therapy in the context of diabetes

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2021 · $403,748

## Abstract

Scope of Work / Abstract
This Administrative Supplement proposal is to investigate the role of inflammasome signaling in
models of Alzheimer's disease (AD) complicated by diabetes mellitus (DM). AD is a progressive
neurodegeneration accounting for 60-70% of all the dementia worldwide. DM, the metabolic
syndrome responsible for a variety of complications including diabetic retinopathy (the subject of
the parent proposal), is characterized by hyperglycemia, hyperinsulinemia, and insulin resistance.
Numerous epidemiologic analyses have identified DM as a significant risk factor and comorbidity
for AD. In addition, DM and AD share inflammasome activation as pathomechanisms, and each
entity has independently been shown to be responsive to inflammasome inhibition. We propose
to test the overall hypothesis that inflammasome inhibition reduces neuroinflammation and
improves cognitive outcomes in mouse AD models that are complicated by the co-morbidity of
DM. To accomplish this, we will critically assess the spatial and temporal kinetics of
inflammasome activation in the brain in combined DM/AD models. In addition, we will test whether
the presence of DM affects the efficacy of inflammasome inhibition on cognitive outcomes of AD
mouse models. As such, this supplement request focused on AD is within the scope of the active
parent NIH award and has the potential to stimulate new studies for examining novel molecular
and biochemical mechanisms of inflammasome activation in AD in the presence of metabolic
disorders. We predict that establishing inflammasome as a key link between DM and AD
will stimulate additional activity on the part of endocrinologists, immunologists, and
neurobiologists thereby leading to progress in deciphering and potentially treating AD and related
dementias complicated by DM. This supplement will also enable our laboratory to develop a focus
on AD and related dementias by generating additional experimental data that can be leveraged
to submit new proposals focused directly on AD and related dementias.

## Key facts

- **NIH application ID:** 10287353
- **Project number:** 3R01EY031039-02S1
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Jayakrishna Ambati
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $403,748
- **Award type:** 3
- **Project period:** 2020-09-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10287353

## Citation

> US National Institutes of Health, RePORTER application 10287353, Inflammasome-based Alzheimer's disease therapy in the context of diabetes (3R01EY031039-02S1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10287353. Licensed CC0.

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