# Sequelae of SARS-CoV-2 Infection in Alzheimer's Disease

> **NIH NIH R01** · SOUTHERN ILLINOIS UNIVERSITY SCH OF MED · 2020 · $368,750

## Abstract

Project Summary/Abstract
The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic
has created a healthcare crisis that was previously reserved for the accelerating Alzheimer’s
disease (AD) diagnoses. Geriatric individuals are a high risk group prone to severe infection and
death, however, a large percentage of these individuals will survive. The predilection of SARS-
CoV-2 and AD to this population indicates age-associated factors may become aggravated upon
viral infection, thereby exacerbating underlying AD symptomatology. We need a better
understanding of the long-term effects of SARS-CoV-2 infection – particularly in relation to AD
progression.
AD is an age-related neurodegenerative disorder characterized by progressive anterograde
amnesia and eventual death. Blood brain barrier (BBB) disruption is typically observed in AD
patients leading to increased vascular permeability. This disrupted microvasculature predisposes
individuals with mild cognitive impairment and AD to increased CNS infiltration by SARS-CoV-2.
Once in the CNS, SARS-CoV-2 can infiltrate host cellular components through interaction with
angiotensin converting enzyme-2 (ACE2). ACE2 is part of the renin-angiotensin system,
expressed on hippocampal neurons, and involved with learning and memory. Downregulation of
ACE2 is observed in AD patients in conjunction with elevated amyloid-β (Aβ) and tau levels.
Further internalization of this receptor upon SARS-CoV-2 neurotropism may exacerbate AD
pathology and potentiate disease progression. Viral infection can also cause host cell senescence
as a defense mechanism against viral replication. The subsequent senescence-associated
secretory phenotype (SASP) can secrete pro-inflammatory cytokines and chemokines impacting
neighboring cells and causing a deleterious feed-forward cycle propagating AD pathology and
cognitive decline.
The Aims of our current funding mechanism are designed to elucidate the role of cellular
senescence in AD. The SARS-CoV-2 emergent crisis coupled with its proclivity to infect geriatric
populations and our scientific understanding of viral infection on senescent cell burden provides
SCIENTIFIC PREMISE for the proposed studies. For this administrative supplement we
hypothesize that CNS infection of SARS-CoV-2 increases senescent cell burden thus aggravating
the development, progression, and severity of cognitive deficits in AD mouse models.
Complimentary in vitro (AIM 1) and in vivo (AIM 2) assays will be used to probe the long-term
consequences of SARS-CoV-2 infection on senescent cell accumulation andneuroinflammation,
thereby accelerating cognitive and physical AD symptomatology.

## Key facts

- **NIH application ID:** 10144789
- **Project number:** 3R01AG061937-03S1
- **Recipient organization:** SOUTHERN ILLINOIS UNIVERSITY SCH OF MED
- **Principal Investigator:** Erin R Hascup
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $368,750
- **Award type:** 3
- **Project period:** 2018-09-30 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10144789

## Citation

> US National Institutes of Health, RePORTER application 10144789, Sequelae of SARS-CoV-2 Infection in Alzheimer's Disease (3R01AG061937-03S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10144789. Licensed CC0.

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