# A geroscience approach for investigating resilience to SARS-CoV-2 pathology in mice with Alzheimer's disease

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2021 · $548,438

## Abstract

Abstract
The parent grant for this supplement application is R01 AG067193, “A geroscience approach for treating
Alzheimer's disease”. The supplement proposal is an extension of the parent grant and is titled “A geroscience
approach for investigating resilience to SARS-CoV-2 pathology in mice with Alzheimers disease”. The
extension is designed to look at the complications of COVID-19 in the presence of cognitive impairment and
neuropathological lesions of Alzheimer's disease in an aging mouse model. This is translationally relevant
because patients with cognitive impairment related to Alzheimer's disease (AD) are at increased risk for
complications of SARS-CoV-2 infection. Several factors are involved including cognitive impairment resulting in
failure to follow exposure guidelines, such as crowd mingling, hand washing and other decontamination
procedures. In addition, many individuals that require various levels of intensive care may come in close
contact with others with similar poor health conditions that may be carrying the virus. Lastly, the debilitating
effects of AD may inherently increase susceptibility to the severe complications of SARS-CoV-2 infection
known to occur in older frail people. For these reasons, it is critical to investigate the mitigating factors
associated with increasing resilience to pathological consequences of infection to prevent increased morbidity
and mortality in an already susceptible elderly population. Given that a major risk factor for developing severe
and fatal SARS-CoV-2 pathology is aging, it is thus a centerpiece for the geroscience concept that examines
the relationship between biological aging and age-related diseases through multiple processes, and that aging
intervention requires targeting multiple aging processes. Our parent grant is set up to address this concept for
AD. The development of a multidrug cocktail that targets multiple aging processes and increases resilience to
AD pathology should, by definition, also increase resilience to SARS-CoV-2 pathology in AD patients. The
hypothesis of this supplement proposal is that a drug cocktail of rapamycin, acarbose, and
phenylbutyrate, targeting multiple aging processes, will increase resilience to the pathological
consequences of SARS-CoV-2 infection in an aging mouse model of AD. Aim 1 will investigate effects of
treatment with an anti-aging drug cocktail in AD mice infected with SARS-CoV-2. Aim 2 will develop pathology
profiles to show that treatment of AD mice with an anti-aging drug cocktail will enhance resilience and improve
health by targeting processes of aging and prevent the devastating pathology caused by SARS-CoV-2
infection. This approach has tremendous clinical health implications for AD patients but perhaps just as
important for individuals in the early stage of disease such as mild cognitive impairment. The concept of a drug
cocktail that could successfully increase resilience to COVID-19 pathology in Alzheimers disease patients
would b...

## Key facts

- **NIH application ID:** 10197633
- **Project number:** 3R01AG067193-02S1
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Martin C Darvas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $548,438
- **Award type:** 3
- **Project period:** 2020-04-15 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10197633

## Citation

> US National Institutes of Health, RePORTER application 10197633, A geroscience approach for investigating resilience to SARS-CoV-2 pathology in mice with Alzheimer's disease (3R01AG067193-02S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10197633. Licensed CC0.

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