# The contribution of perivascular macrophages to cerebral microvascular dysfunction in Alzheimer's

> **NIH NIH R01** · ROSALIND FRANKLIN UNIV OF MEDICINE & SCI · 2021 · $336,800

## Abstract

PROJECT SUMMARY
Obesity, inflammation and cerebral microvascular dysfunction are highly interdependent risk factors for
Alzheimer’s disease. However, the mechanistic understanding of how these risk factors interact to influence
the progression of Alzheimer’s is limited. This gap will be addressed by the current administrative supplement.
Preliminary data and published studies from the applicant’s lab show that outside of the brain, macrophages
are the dominant inflammatory mediator driving microvascular dysfunction in obesity. Intriguingly,
macrophages are also present within the brain, where they are localized to the perivascular space surrounding
the penetrating arterioles of the cerebral microvasculature, although their contribution to vascular function and
Alzheimer’s progression is poorly defined. The current objective is to assess how perivascular macrophages
are involved in the interaction between obesity and Alzheimer’s. The objective will be accomplished by testing
the central hypothesis that obesity-dependent inflammation contributes to the progression of Alzheimer’s
disease by increasing cerebral microvascular dysfunction. Two specific aims are proposed: aim 1 will define
how obesity and inflammation contribute to cerebral microvascular dysfunction in Alzheimer’s Disease, and
aim 2 will define how perivascular macrophages contribute to Alzheimer’s Disease pathology. Diet-induced
obesity will be studied in a transgenic mouse model of Alzheimer’s. The interaction between obesity,
inflammation and the cerebral microvasculature will be assessed in both male and female animals using
macrophage phenotype analysis, macrophage depletion studies, in vivo deep brain imaging microscopy, and in
vitro functional assays of freshly isolated penetrating arteriolar segments. Completing these aims will address
the question of why obesity is a risk factor for Alzheimer’s disease by establishing a new mechanism in which
inflammation exacerbates Alzheimer’s through macrophage-dependent cerebral microvascular dysfunction.

## Key facts

- **NIH application ID:** 10288760
- **Project number:** 3R01HL142906-03S1
- **Recipient organization:** ROSALIND FRANKLIN UNIV OF MEDICINE & SCI
- **Principal Investigator:** Carl White
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $336,800
- **Award type:** 3
- **Project period:** 2019-01-19 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10288760

## Citation

> US National Institutes of Health, RePORTER application 10288760, The contribution of perivascular macrophages to cerebral microvascular dysfunction in Alzheimer's (3R01HL142906-03S1). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10288760. Licensed CC0.

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