Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Alzheimer's Disease and Related Dementia-like Sequelae of SARS-CoV-2 Infection: Virus-Host Interactome, Neuropathobiology, and Drug Repurposing

Award Number: R01AG082211
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/15/2023
PERIOD OF PERFORMANCE END DATE: 04/30/2028

Group Awards By:

View Award Description

Alzheimer's Disease and Related Dementia-like Sequelae of SARS-CoV-2 Infection: Virus-Host Interactome, Neuropathobiology, and Drug Repurposing - PROJECT SUMMARY Abundant cross-interdisciplinary evidence indicates that there are multiple pathophysiological processes driving development and progression of Alzheimer’s disease (AD) and AD-related dementias (ADRD), including neuroinflammation and microvascular injury to pathogens, especially viruses. We are examining these aspects of AD/ADRD with respect to human coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with over 87 million cases in the United States alone. Notably, substantial evidence indicates neurocognitive sequelae of COVID-19, which are poised to ultimately lead to a surge in cases of AD/ADRD, and other forms of neurocognitive impairment. Preliminary evidence from our team identified that SARS-CoV-2 infection caused neuroinflammation and brain microvascular injury, two major risk factors for AD/ADRD. We have also demonstrated that systematic characterization of human- and virus- human protein interactome maps can identify novel pathophysiological pathways and drug targets to protect the SARS-CoV-2-infected brains. We therefore posit that multimodal analyses of SARS-CoV-2-human interactome maps in patient induced pluripotent stem cell (iPSC)-derived brain microvascular endothelial cells (BMECs) and brain single-nucleus genomic/epigenomic data from de novo AD/ADRD-like neurocognitive impairment in COVID-19 patients (Neurocogn-COVID), will provide valuable unbiased insights into the complex etiology of neurocognitive sequelae of SARS-CoV-2 at molecular, cellular and network levels. This project will elucidate critical understanding of both brain cell type-specific virus-human protein interactome-inhibitory targets and neuro-immune gene networks and brain microvascular injury that may lead to AD/ADRD after viral infection. Our immediate goal is to build a comprehensive, brain cell type-specific virus-human protein interactome map for identifying molecular drivers for neurocognitive sequelae of SARS-CoV-2 infection using our high-throughput protein interactomics platform. Aim 1 will interrogate the SARS-CoV-2 virus-human interactome to identify and validate molecular drivers of ADRD-like viral microvascular injury in iPSC-derived BMECs (age-, sex-, APOE- matched iPSC lines). Aim 2 will interrogate cell type-specific neuroimmune and brain endothelial transcriptional networks to identify pathophysiology related to virus-induced neuro-inflammation and brain microvascular injury. We will leverage single-nucleus genomic/epigenomic data generated from brain tissues of donors who suffered from neurocogn-COVID, AD, mild cognitive impairment (MCI), and age-, sex-, APOE-matched healthy controls from the Cleveland Alzheimer's Disease Research Center (ADRC) and Northwestern ADRC. Aim 3 will test the hypothesis that potential new opportunities for drug repurposing in neurocognitive sequelae can be identified through a combination of longitudinal population-based validation and functional testing in mouse models. Successful completion of this project will elucidate mechanistic biomarker for neurocognitive sequelae of SARS- CoV-2 and identify new drug targets and treatments to be directly tested in clinical trials. 1


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $780,748 )
2026	2026	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Aging Research	000	2	5/11/2026	EXTENSION WITH OR WITHOUT FUNDS	$780,748
														Subtotal = $780,748

Grand Total All Awards = $780,748

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Alzheimer's Disease and Related Dementia-like Sequelae of SARS-CoV-2 Infection: Virus-Host Interactome, Neuropathobiology, and Drug Repurposing

Award Number: R01AG082211

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/15/2023

PERIOD OF PERFORMANCE END DATE: 04/30/2028

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer