# Elucidating changes in astrocyte subpopulations associated with resistance to Alzheimers Disease pathology in multi-ethnic cohorts

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $745,434

## Abstract

Project Summary/Abstract
Alzheimer’s Disease (AD) is a progressive neurodegenerative disease, manifesting in brain
pathology, neuropsychiatric symptoms, and cognitive decline. In general, confirmatory
diagnosis of AD involves both pathological hallmarks (such as plaques and tangles) as well
as clinically observed cognitive decline. Whereas most cases of patients with AD pathology
show cognitive and clinical phenotypes, a subset of individuals have pathology suggestive of
AD without the corresponding cognitive impairment. One possible explanation is that these
“resistant” individuals have compensatory mechanisms protecting their cognitive status from
the presence of pathology. Recent work from single-nucleus RNA-sequencing on post-
mortem human frontal cortex tissue suggests molecularly distinct subsets of astrocytes (a
non-neuronal cell type in the brain) are differentially present in “resistant” versus
“susceptible” (cognitively declined with pathology) individuals. However, this observation so
far has been limited to a single brain region in a small sample of primarily Caucasian
individuals. This proposal aims to corroborate and extend this finding by investigating
astrocyte subpopulations, their molecular profiles, and their associations with other cell types
in multiple regions of the brain in an ethnically diverse. Through a combination of single-
nucleus RNA-sequencing, spatial transcriptomics, immunohistochemistry, and systems
biology, we propose to create a map of the differential distribution of astrocyte
subpopulations in “resistant” and “susceptible” individuals, their spatial relation to pathology
and other cell types, and candidate genes and pathways that involved in astrocyte-mediated
resistance to tau pathology. Ultimately, characterizing the association between specific
astrocyte subpopulations, their interactions, and pathways involved in resistant individuals
may identify therapeutic avenues to mitigate cognitive decline in the presence of AD
pathology.

## Key facts

- **NIH application ID:** 10162469
- **Project number:** 5R01AG066831-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Vilas Menon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $745,434
- **Award type:** 5
- **Project period:** 2020-05-15 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10162469

## Citation

> US National Institutes of Health, RePORTER application 10162469, Elucidating changes in astrocyte subpopulations associated with resistance to Alzheimers Disease pathology in multi-ethnic cohorts (5R01AG066831-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10162469. Licensed CC0.

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