# Relating Neuroimmune and Neurovascular Alterations During Alzheimer's Disease Progression

> **NIH NIH R01** · NORTHEASTERN UNIVERSITY · 2021 · $528,916

## Abstract

ABSTRACT
This project will explore how alterations in neuroimmune interactions, neurovascular signaling, and cerebral
metabolism contribute to Alzheimer's disease (AD) pathology, along with the potential benefits of exercise (aka
physical activity). Given the rapid, aggressive deterioration in cognition and function following clinical prognosis
and the dire threat that AD poses to the rising aging population, the current lack of therapeutic techniques and
early, robust diagnostic markers of AD onset and progression constitutes a critical challenge for modern
healthcare. In addition to strongly associated pathological hallmarks such as accumulation of amyloid-β
oligomers/plaques and neurofibrillary tangles, AD progression involves a pronounced neuroinflammatory
response from CNS cells like microglia and astrocytes, as well as impairments to cerebral blood flow, energy
metabolism, and cellular signaling. These processes reportedly initiate several years before the first symptoms
of cognitive decline become evident. Because no individual preclinical AD symptom correlates perfectly with
cognitive impairment, untangling the relationships and interdependencies between these pathological alterations
is necessary to better understand the complex pathogenesis of AD, and it requires characterization of intricate
cellular and vascular interactions with high spatial resolution in living brains of preclinical models. Furthermore,
although the protective mechanisms remain unclear, physical activity shows promise for reducing the likelihood
and severity of cognitive impairment in elderly subjects. Using a broad assortment of custom-designed advanced
microscopy methods, we will explore, at the cellular and microvascular level, how seemingly distinct
neuroimmune and cerebrovascular changes are interrelated and how they collectively contribute to the
devastating AD-related neurodegeneration in preclinical mouse models of AD. We will also investigate how
physical activity can mitigate these neuroimmune and neurovascular alterations. The results will help us
understand in much greater detail the multifaceted structural and functional changes that ensue in the brain over
the ~2 decades before clinically-observable cognitive deficiencies manifest, and they will help guide new early
intervention and treatment strategies to minimize AD-related cognitive degradation.

## Key facts

- **NIH application ID:** 10227257
- **Project number:** 5R01AA027097-04
- **Recipient organization:** NORTHEASTERN UNIVERSITY
- **Principal Investigator:** Mohammad Abbas Yaseen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $528,916
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10227257

## Citation

> US National Institutes of Health, RePORTER application 10227257, Relating Neuroimmune and Neurovascular Alterations During Alzheimer's Disease Progression (5R01AA027097-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10227257. Licensed CC0.

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