# Effects of apoE Isoform, Sex and Diet on Insulin Regulation in Brain

> **NIH NIH RF1** · SEATTLE INST FOR BIOMEDICAL/CLINICAL RES · 2020 · $376,250

## Abstract

Project Summary
Severe acute respiratory syndrome-coronavirus (SARS-CoV-2) causes a world-wide pandemic
involving a cytokine storm. Besides direct action at the lung and heart, SARS-CoV-2 has also
been shown to cross the blood-brain barrier (BBB), being recovered from cerebrospinal fluid
(CSF) and brain tissue. Its ability to invade the brainstem and so affect central nervous system
(CNS) control of breathing may contribute to its ability to induce respiratory failure. There are
several reasons why Alzheimer’s disease (AD) patients are at a special risk for COVID-19. Age
is a significant risk factor, where the elderly are more susceptible to COVID-19 by being more
likely to progress to severe disease, showing increased mortality and different clinical features
than young and middle-aged patients. The combination of COVID-19 and dementia, another
pandemic currently present in our aging society, is being considered a “double hit” and raises
concerns regarding dementia care during COVID-19. SARS-CoV-2 has 3 viral envelope proteins
(S, E, and M) with the S being the protein that mediates attachment to the host cell, capable of
fusing to the angiotensin converting enzyme 2 receptor (ACE2R). Several lines of evidence link
ACE and the apolipoprotein E (apoE) isoform, E4, another risk factor for developing AD. While
working directly with the SARS-CoV-2 virus is valuable, it requires working in an ABSL-3 level
facility and substantially restricts studies with non-perfused tissues. SARS-CoV-2 recombinant
virus-like particles (VLPs) offer an attractive way to study the pathogenesis of SARS-CoV-2 in
animals, without the involvement of replicating viruses. In this application, using mice expressing
human E3 or E4 under control of the mouse apoE promoter, we will investigate the mechanisms
by which apoE isoform, sex, and age can affect SARS-CoV-2 VLP transport across the BBB and
impact on cognition.

## Key facts

- **NIH application ID:** 10152983
- **Project number:** 3RF1AG059088-01S1
- **Recipient organization:** SEATTLE INST FOR BIOMEDICAL/CLINICAL RES
- **Principal Investigator:** WILLIAM A BANKS
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $376,250
- **Award type:** 3
- **Project period:** 2018-06-05 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10152983

## Citation

> US National Institutes of Health, RePORTER application 10152983, Effects of apoE Isoform, Sex and Diet on Insulin Regulation in Brain (3RF1AG059088-01S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10152983. Licensed CC0.

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