# Role of inflammasomes in Alzheimer's Disease

> **NIH NIH R01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2020 · $280,148

## Abstract

PROJECT ABSTRACT
Supplement to R01 AG059752-03:
Neuroinflammation is an important component of Alzheimer's disease (AD) and Fronto-temporal dementia
(FTD). However, the molecular mechanism by which inflammation modulates AD and FTD progression are not
defined. We discovered that both AD and FTD patients uniformly have evidence of activated inflammasomes in
their brains. We have also found that systemic inflammation promotes AD disease and increases the
deposition of Ab plaques, in part by reducing microglial clearance of Aβ in the brain. This process was
dependent on inflammasomes, as NLRP3 KO mice showed clear protection with nearly normalized microglial
morphology and Aβ clearance. We have also noted that NLRP3 inflammasome activation drives tau pathology
by inducing tau hyper-phosphorylation. Taken together, these observations suggest that systemic
inflammation likely contributes to neurologic diseases, particularly AD and FTD, by promoting the accumulation
of Ab plaques and inducing the phosphorylation and aggregation of tau in neurofibrillary tangles.
Acute COVID-19 is associated with a hyper-inflammatory cytokine storm and more than a third of patients
develop neurologic symptoms. We believe that acute COVID-19 driven inflammation will aggravate pre-
existing neurologic disorders, such as Alzheimer’s Disease (AD) and fronto-temporal dementia (FTD) via
activation NLRP3 inflammasomes and downstream inflammasome-dependent cytokines in the brain.
Successful completion of this supplemental Aims will elucidate the role of inflammasome-generated cytokines
in COVID-19 associated neurologic symptoms and could result in novel translational approaches designed to
specifically halt the inflammation that drives neuroinflammation in this disease. We also hypothesize that
COVID-19 inflammation can potentially accelerate cognitive decline in AD and FTD patients. This study has
the potential to identify therapeutic targets to prevent the neurologic disorders that occur in many COVID-19
hospitalized patients and to determine the impact of COVID-19 inflammation on AD and FTD pathology and
disease progression.

## Key facts

- **NIH application ID:** 10167924
- **Project number:** 3R01AG059752-03S1
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Douglas T Golenbock
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $280,148
- **Award type:** 3
- **Project period:** 2018-08-15 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10167924

## Citation

> US National Institutes of Health, RePORTER application 10167924, Role of inflammasomes in Alzheimer's Disease (3R01AG059752-03S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10167924. Licensed CC0.

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