# Small vessel disease contributions to neurodegeneration in Alzheimer's disease

> **NIH NIH K01** · RUSH UNIVERSITY MEDICAL CENTER · 2023 · $112,463

## Abstract

PROJECT SUMMARY/ABSTRACT
Brain atrophy is a common correlate of dementia. Majority of older persons with dementia have comorbid
cerebral small vessel disease (SVD) and Alzheimer’s disease (AD) pathology. The spectrum of SVD includes
both small vessel pathologies and diverse tissue injuries. Differing biologic processes may contribute towards
the etiology of brain atrophy in vulnerable brain regions, including the hippocampus, a structural brain change
seen on MRI proximate to cognitive decline. The interplay between SVD and AD is complex, with evidence to
suggest microglia inflammation may be important. To date, very little research has focused on the interplay
between SVD, AD, and microglia inflammation in the context of regional brain volume. The objective of this study
is to examine the association of neuropathologic and MRI SVD markers with regional brain volumes and identify
the effects of comorbid AD pathology and microglia inflammation. This K01 will integrate neuropathology,
neuroimaging, and cognitive data from three community-based studies, the Religious Orders Study, the Memory
and Aging Project, and Minority Aging and Research Study. Specifically, this proposal will use state-of-the-art
methods to capture novel digital morphometric changes from post-mortem brain tissue, use MRI-defined
quantitative volume measures in susceptible brain regions, examine differing SVD markers with regional brain
volumes, examine in-vivo longitudinal SVD changes, and extend analyses in African Americans. Primary aims
are 1) Examine the relationship between SVD markers, AD pathology, and regional brain volume, 2) Determine
the role of microglia inflammation with SVD markers and regional brain volume, and 3) Identify associations
between SVD markers, regional brain volume, and cognitive decline. An exploratory aim 4) will examine the
relationship between SVD markers and regional brain volume in African Americans. My mentorship team has
extensive experience with large epidemiological studies of aging and dementia and will provide expert guidance
through the research methods and complimentary training plan. Specific areas of mentorship expertise include
translational neuropathology, neuroimaging, biostatistics, health disparities, and cognition . Their expertise will
be augmented by the interdisciplinary training programat Rush Alzheimer’s Disease Center (RADC), and cutting-
edge resources within the RADC Cores (Neuropathology, Neuroimaging and Biomarker, and Biostatistics).
Together, the proposed research and training plan provides the framework from which I can launch a successful
independent research career.

## Key facts

- **NIH application ID:** 10677799
- **Project number:** 5K01AG075177-02
- **Recipient organization:** RUSH UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Alifiya Kapasi
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $112,463
- **Award type:** 5
- **Project period:** 2022-08-15 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10677799

## Citation

> US National Institutes of Health, RePORTER application 10677799, Small vessel disease contributions to neurodegeneration in Alzheimer's disease (5K01AG075177-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10677799. Licensed CC0.

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