# Spatial analysis of regional, cell type and molecular hallmarks of Alzheimer's disease

> **NIH NIH U19** · ALLEN INSTITUTE · 2020 · $1,022,666

## Abstract

ABSTRACT (PROJECT 3)
The molecular mechanisms underlying cellular vulnerability in Alzheimer’s disease are unclear. The objective
of this project is to clarify the molecular mechanisms responsible for select cell vulnerability and pathogenesis
by applying spatial methods for highly multiplexed RNA and protein analysis in Alzheimer’s-affected tissue
sections. We will optimize and standardize platforms for multiplexed fluorescence in situ hybridization (mFISH)
to examine AD-linked gene sets derived from single nucleus transcriptome analysis, as well as
immunohistochemistry (IHC) to examine pathological protein markers in the context of cell type populations in
intact human brain tissue. These methods will then be applied to Alzheimer’s disease tissues from brain
regions affected in different levels of disease severity to understand 1) the spatial organization of
transcriptomically-defined cell types in these brain regions and changes in this organization with disease
severity (e.g. selective vulnerability or proliferation), 2) molecular pathways disrupted in Alzheimer’s disease in
the context of specific cell types, and 3) the relationship between these affected cell types and the markers of
Alzheimer’s pathology, such as amyloid precursor protein and hyperphosphorylated tau. These data generated
by mFISH and IHC together will provide a high-resolution map of the cellular and molecular consequences of
clinically typical Alzheimer’s disease and an enhanced view of Alzheimer’s pathology, as well as a powerful
technology platform for future analyses of larger and more varied cohorts.

## Key facts

- **NIH application ID:** 9855878
- **Project number:** 1U19AG060909-01A1
- **Recipient organization:** ALLEN INSTITUTE
- **Principal Investigator:** Ed Lein
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,022,666
- **Award type:** 1
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9855878

## Citation

> US National Institutes of Health, RePORTER application 9855878, Spatial analysis of regional, cell type and molecular hallmarks of Alzheimer's disease (1U19AG060909-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9855878. Licensed CC0.

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