# Project 3: 3-D Molecular Atlas of cerebral amyloid angiopathy in the aging brain with and without co-pathology

> **NIH NIH U19** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2024 · $504,727

## Abstract

PROJECT 3: PROJECT SUMMARY/ABSTRACT
Cerebral amyloid angiopathy (CAA) is an age-associated vasculopathy in which there is deposition of
amyloid-β protein in the walls of leptomeningeal and parenchymal blood vessels. It can be seen in association
with Alzheimer’s disease- neuropathologic change (AD-NC), as well as in isolation. In this study, we focus
on how CAA alters the local cellular environment in three distinct regions of the brain that are known to have
variable susceptibility to CAA: superior temporal gyrus, dorsolateral prefrontal cortex, and calcarine cortex.
We will compare CAA in isolation and in association with increasing burden of AD-NC. There is extremely
limited molecular data on how CAA can modify the local cellular environment in aging, although we know
CAA can cause cognitive decline in the absence of any other proteinopathy, but can also exacerbate the
cognitive decline with proteinopathy. Thus, the overarching goal of this project is to generate a spatial atlas
of cell types and molecular signatures in cases with CAA and variable severities of Alzheimer’s Disease-
Neuropathologic Change (AD-NC) to assess short- and long-range, and interactive effects of multiple
pathologies on cellular composition and signatures from post-mortem human brain tissue. We hypothesize
that CAA has local effects on the cell type composition and protein signature nearby, affecting all elements
of the neurovascular unit (NVU), and that the effects of CAA are exacerbated by the presence of comorbid
AD proteinopathies. For this project we propose a combination of novel but demonstrably scalable protein
and gene expression approaches, to study large volumes (300-micron thickness) of human tissue with
combinations of CAA with and without AD-NC. This will allow for the generation of a high-resolution atlas of
cell types and gene expression signatures in aged human brain tissue that relate to CAA, complementing
many of the existing and ongoing bulk and single-nucleus RNA-seq studies in the field of human
neurodegeneration research

## Key facts

- **NIH application ID:** 10935941
- **Project number:** 5U19AG074862-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Julie A. Schneider
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $504,727
- **Award type:** 5
- **Project period:** 2023-09-30 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10935941

## Citation

> US National Institutes of Health, RePORTER application 10935941, Project 3: 3-D Molecular Atlas of cerebral amyloid angiopathy in the aging brain with and without co-pathology (5U19AG074862-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10935941. Licensed CC0.

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