# Project 1: 3-D Molecular atlas of the aging brain

> **NIH NIH U19** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2024 · $598,754

## Abstract

PROJECT 1: PROJECT SUMMARY/ABSTRACT
Aging is characterized by the accumulation of molecular and cellular damage resulting in decreasing cellular
functionality; diseases that are particularly associated with aging include cerebrovascular disease and
neurodegenerative diseases. Although focus has been on individual proteinopathies and cerebrovascular
defects that occur more frequently with age, little is known about the local effects of aging on gene expression
signatures and how these effects impact cellular composition and increase susceptibility to disease. Here,
we focus on how ageing alters the cellular environment in three distinct regions of the brain, in patients with
minimal or no pathology, that are known to be susceptible to the effects of protein and/or vascular pathologies
in later life: superior temporal gyrus, dorsolateral prefrontal cortex, and calcarine cortex. We hypothesize that
normal aging will have local and global effects on cell type composition and associated gene
expression/molecular signatures, and that understanding these attributes will allow us to form a better
understanding of why divergence from this state may result in pathology in these vulnerable regions. The aim
of this project is to generate a spatial atlas of normal aging using individuals spanning an age range from 20-
90, all with minimal to no underlying pathology. To achieve this goal, we will use immunohistochemical (4i)
and unbiased transcriptomics (10x Visium ST) techniques to generate a large-volume (300-micron thickness)
3-D atlas of three key brain regions vulnerable to pathology in later life from 30 individuals. We aim to derive
cell type- and molecular signature-specific maps for each subject, integrating these data into a computational
framework to characterize changes in local and global signatures with respect to age. We will then validate
high-value associations derived from this framework in a replication cohort of 20 individuals. Using this
approach, we hope to provide an unprecedented set of cell type and gene expression signature maps that
represent the spectrum of normal aging.

## Key facts

- **NIH application ID:** 10935938
- **Project number:** 5U19AG074862-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Hemali Phatnani
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $598,754
- **Award type:** 5
- **Project period:** 2023-09-30 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10935938

## Citation

> US National Institutes of Health, RePORTER application 10935938, Project 1: 3-D Molecular atlas of the aging brain (5U19AG074862-02). Retrieved via AI Analytics 2026-06-03 from https://api.ai-analytics.org/grant/nih/10935938. Licensed CC0.

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