# Molecular and anatomical characterization of cell types in the aging mouse brain

> **NIH NIH R01** · ALLEN INSTITUTE · 2021 · $1,174,999

## Abstract

Project Summary
One of the most fundamental questions in brain aging research is whether age-related alterations affect all brain
regions equally, or whether some regions, and cell types within those regions, are more vulnerable to the effects
of aging than others. Aging is associated with cognitive decline, and is reported to cause alterations in a variety
of important cellular processes and in a variety of cell types (e.g., microglia, astrocytes, neurons). Broad classes
of cells in affected brain regions are known to be selectively vulnerable to age-related neurodegenerative
diseases, but the specific molecular mechanisms underlying this vulnerability are unclear. An essential
prerequisite to understanding this selective vulnerability is to understand the detailed changes at cell type and
circuit levels during the aging process. Cataloging brain cell types and their connectivity in normal aging brain is
foundational to uncovering the mechanisms and therapeutic opportunities for age-related brain disorders.
State-of-the-art single-cell technologies, in particular single-cell transcriptomics with its high dimensional
molecular information, but also spatial transcriptomics, single-cell epigenomics and single-cell morphology, are
providing transformative information about brain cell types at an unprecedented scale and resolution. We
propose to utilize our well-established omics pipelines to characterize and classify cell types in 18 months old
male and female C57BL/6J mice and compare the results with the extensive brain-wide datasets in young adult
(~P56) mice already being generated in the current BRAIN Initiative Cell Census Network (BICCN). We will use
single-nucleus transcriptomics and epigenomics to obtain a high-level survey of neuronal and non-neuronal cell
classes/types across the entire mouse brain, and then an in-depth single-cell and spatial transcriptomic study in
brain areas showing age-related changes and/or vulnerable to neurodegenerative diseases. We will utilize our
imaging–based registration process to map all data into the Common Coordinate Framework (CCF), which
allows accurate cross-age quantitative comparisons that will be crucial for uncovering age-related changes. By
conducting concurrent single-cell gene expression and chromatin accessibility measurements in the same brain
regions, and a detailed spatial transcriptomic map of the proportion and distribution of different cell types and
specific molecular pathways, we will chart an integrated path towards gaining mechanistic insight underlying the
cognitive decline in aging and age-related disease pathology.

## Key facts

- **NIH application ID:** 10264014
- **Project number:** 5R01AG066027-03
- **Recipient organization:** ALLEN INSTITUTE
- **Principal Investigator:** Bosiljka Tasic
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,174,999
- **Award type:** 5
- **Project period:** 2019-09-30 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10264014

## Citation

> US National Institutes of Health, RePORTER application 10264014, Molecular and anatomical characterization of cell types in the aging mouse brain (5R01AG066027-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10264014. Licensed CC0.

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