# Cerebrovascular Remodeling and Neurodegenerative Changes in Alzheimer's Disease

> **NIH NIH R01** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2022 · $824,997

## Abstract

PROJECT SUMMARY
Alzheimer’s disease, the most common cause of dementia and the sixth most common cause of death, afflicts
nearly 6 million people in the United States. Alzheimer’s disease is a major economic burden to our society with
an annual cost of more than $250 billion. Cerebrovascular integrity is critical for proper metabolism and perfusion
of the brain. Compliance of large cerebral arteries is critical as these arteries dampen the pulsatile pressure and
protect the microcirculation and blood brain barrier from damage. Cerebrovascular dysfunction can have
detrimental impacts on the brain. Growing evidences suggest that cerebrovascular dysfunction plays a crucial
role in the pathogenesis of Alzheimer’s disease and can potentially be used as a biomarker for preclinical
Alzheimer’s disease. The overall goal of this project is to unravel the close relationship between cerebrovascular
remodeling and the progression of Alzheimer’s disease.
 Our preliminary study suggested that with pathological progression of Alzheimer’s disease, the human
cerebral artery showed progressive stiffening, structural breakdown, and increases smooth muscle cell atrophy.
We thus hypothesize that the structural and functional changes in large cerebrovasculature is correlated with
neurodegeneration and the accumulation of Amyloid-β, other toxic metabolites, and tau pathology in the brain.
Building upon our multidisciplinary expertise in vascular mechanobiology, precision mass spectrometry,
advanced optical imaging, immunohistochemistry, vascular biology and neuropathology of Alzheimer’s disease,
we will test this hypothesis in three aims: Aim 1) to determine cerebrovascular remodeling (biomechanical,
structural, and compositional changes) in the frontal and temporal lobes in Alzheimer’s disease; Aim 2) to
determine the association between cerebrovascular remodeling and Alzheimer’s disease pathological changes
in the frontal and temporal lobes of the brain; and Aim 3) to examine the association between cerebrovascular
remodeling and antemortem cognitive status and neuropsychological test performance.
We will use no or low atherosclerotic cerebrovascular and brain tissue from 100 age- and sex-matched brain
donors from the NIA-funded BU Alzheimer’s Disease Research Center with 1) no Alzheimer’s disease pathology,
2) low Alzheimer’s disease pathology, and 3) intermediate/high Alzheimer’s disease pathology
. These
brain
donors have completed annual National Alzheimer’s Coordinating Center Uniform Data Set evaluations during
life and have available consensus-based cognitive diagnoses. This proposal is designed to leverage existing
resources to make new discoveries. The matched and parallel studies of cerebral vessels and brain tissue will
provide new understandings of the temporal development of cerebrovascular remodeling and AD. Understanding
the role of vascular remodeling in Alzheimer’s disease may lead to the discovery of new treatment options and
directions for interven...

## Key facts

- **NIH application ID:** 10370614
- **Project number:** 1R01AG075876-01
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** Thor Stein
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $824,997
- **Award type:** 1
- **Project period:** 2022-02-01 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10370614

## Citation

> US National Institutes of Health, RePORTER application 10370614, Cerebrovascular Remodeling and Neurodegenerative Changes in Alzheimer's Disease (1R01AG075876-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10370614. Licensed CC0.

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