# Understanding the protective and neuroinflammatory role of human brain immune cells in Alzheimer Disease

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2021 · $338,022

## Abstract

PROJECT SUMMARY
Alzheimer's disease (AD) is a devastating neurodegenerative disease that deeply impacts the quality of life both
socially and financially for affected ones and their relatives. Despite extensive clinical and genomic studies, the
exact mechanisms of development and progression of AD remain elusive. Microglia and other myeloid origin
cells, collectively known as human brain immune cells (HBICs), have been identified to play crucial roles in the
pathogenesis of AD. This is supported through genetic association studies, where many of the common and rare
risk loci affect genes that are preferentially or selectively expressed in HBICs, emphasizing the pivotal role of the
innate immune system in AD. In the parent grant 1R01AG065582, we utilize fluorescence-activated cell sorting
to isolate CD45+/CD11b+ HBICs from human brain fresh tissue. We then apply innovative neurogenomics and
single-cell approaches to generate comprehensive, high-throughput, multi-omics molecular profiles of HBICs
from 300 donors at different stages of AD. These remarkable resources can provide critical insights into the role
of immune cells in AD by increasing our mechanistic understanding of dysfunction in AD risk loci. One critical
component that is currently not addressed in the parent grant is to apply innovative genomic approaches using
AI/ML techniques, which can harmonize the signals from different omics modalities and offer a novel insight into
the role of microglia and other immune cells in AD.
In this Supplement, to increase the utility of the data, we propose to develop and maintain a shared resource of
high-dimensional HBIC omics data for AI/ML applications. In addition, we propose to build a multi-scale
integrative deep learning model leveraging single-cell omics data, to demonstrate the utility of the resource and
serve as a benchmark for others to provide a quantitative measure of performance. This model will help us to
identify protective and neuroinflammatory HBIC subpopulations and colocalize transcriptomic and regulatory
signatures at different stages of AD. The proposed work will address potential challenges in the development of
AI/ML applications. We propose: (1) identifying and removing potential sources of technical variations and
normalize the data (2) uniformly processing and preparing fully annotated AI/ML-ready resource in a self-
contained form for rapid prototyping with modern AI/ML tools (3) sharing and collaborating ideas using an open
forum using AD knowledge base portal. Successful completion of the proposed studies will: (1) facilitate access
to large-scale, multidimensional datasets on HBICs for AI/ML applications; (2) accelerate researches for an
increased mechanistic understanding of the onset and progression of AD; (3) provide systems-level insights
about transcriptional regulation in HBICs and AD pathogenesis using integrative AI/ML model; (4) provide a
prioritized list of significant loci and genes for future mechanistic stu...

## Key facts

- **NIH application ID:** 10412322
- **Project number:** 3R01AG065582-02S1
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** VAHRAM HAROUTUNIAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $338,022
- **Award type:** 3
- **Project period:** 2020-02-15 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10412322

## Citation

> US National Institutes of Health, RePORTER application 10412322, Understanding the protective and neuroinflammatory role of human brain immune cells in Alzheimer Disease (3R01AG065582-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10412322. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*