# Functionally guided adult whole brain cell atlas in human and NHP

> **NIH NIH UM1** · ALLEN INSTITUTE · 2024 · $90,150

## Abstract

Abstract:
The goal of this supplement is to investigate the cellular composition and regulatory mechanisms within the
entorhinal cortex (EC) that vary with age and sex, with a focus on their potential implications for differential
Alzheimer's disease (AD) etiology. The EC is the gateway between the hippocampus and neocortex, and is
therefore a crucial structure for the formation and retrieval of memories. The EC is particularly involved in spatial
memory, navigation and the perception of time, and is among the first brain regions affected by Alzheimer’s
Disease (AD). This proposal seeks to analyze single nucleus (sn)RNA-seq data from 135 macaque entorhinal
cortices, encompassing the natural lifespan of free-living macaques and consisting of 77 females, to identify
variations in cellular composition and gene expression associated with age and sex.
The research plan for this project uses snRNA-seq data, facilitating the investigation of heterogeneity of cell
types and transcriptional states across ages and sexes. The project will generate a comprehensive analysis of
which cell types and gene regulatory networks are most strongly impacted by these demographic factors. This
information will be leveraged to enhance our understanding of the cellular and molecular etiology of AD, with a
particular focus on why females are disproportionately affected.
This proposal also focuses on the scientific training and career development of Kelsi Watkins during her graduate
studies. Kesi will receive training in computational, statistical, and theoretical analysis of large-scale snRNA-seq
data. She will also gain experience and mentorship in public speaking, scientific and professional writing, and
project management, with mentorship provided by experts in bioinformatics and statistical approaches to single-
cell genomics data analysis, who have successfully trained predoctoral and postdoctoral researchers. This
training and development will prepare Kelsi for a successful career as an independent researcher in
neurogenomics and the biology of aging.
The insights gained from this research have the potential to shed light on the disproportionate impact of AD on
females and provide crucial data for addressing the increasing prevalence of the disease in an aging global
population. By elucidating the influence of demographic factors on AD etiology and equipping the next generation
of researchers with essential skills, this project contributes significantly to addressing the pressing challenges
posed by AD in an aging global population.

## Key facts

- **NIH application ID:** 11061630
- **Project number:** 3UM1MH130981-03S2
- **Recipient organization:** ALLEN INSTITUTE
- **Principal Investigator:** Ed Lein
- **Activity code:** UM1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $90,150
- **Award type:** 3
- **Project period:** 2022-08-22 → 2025-04-24

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11061630

## Citation

> US National Institutes of Health, RePORTER application 11061630, Functionally guided adult whole brain cell atlas in human and NHP (3UM1MH130981-03S2). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11061630. Licensed CC0.

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