# Role of perictyte nanotubes in age-related neurovascular dysfunction

> **NIH NIH R21** · BAYLOR COLLEGE OF MEDICINE · 2022 · $454,999

## Abstract

PROJECT SUMMARY
Alzheimer’s disease and Alzheimer’s disease associated dementias are characterized by marked alterations in
neural function and associated cognitive decline. Though changes to neurons themselves are important, recent
findings by our group and others suggest another major contributor to pathogenesis: alterations to
neurovascular coupling. In Alzheimer’s disease, signaling between neurons and vessels appears to break
down, accompanied by defects in vessel responses, cerebral amyloid angiopathy, and structural vascular
alterations. However, little is known about the cellular or molecular basis of these changes. In this proposal, we
identify a key mechanism responsible for maintaining vessel integrity in the context of aging and Alzheimer’s
using the superbly tractable murine retina. We have shown that different retina neuron types exhibit distinct
age- and Alzheimer’s disease-related dystrophies, and that dopaminergic neurons are a central target. In
parallel, our data now reveal that neural changes are accompanied by distinct vascular dystrophies, with
particular disruption to pericytes and their novel nanotube-like processes. Further, using genetic and
pharmacological methods we and others have shown that dopamine can directly influence vascular
organization and function and signal to pericytes. These data suggest that Alzheimer’s disease alters neuro-
vascular coupling via declines in dopamine driven pericyte structure and function. In Aim 1, we determine how
Alzheimer’s disease regulates vasculature structure and function, with a particular focus on pericytes. We test
the hypothesis that pericyte alterations are accompanied by functional declines in vascular hemodynamics,
loss of coupling nanotubes, and locally associated neural decline. In Aim 2, we examine the neural signaling
defects causal to vascular structure and functional declines. Our preliminary data suggest that dopaminergic
neurons are reduced in Alzheimer’s disease, and that dopamine is required for maintaining vessel integrity.
We thus test the idea that declines in dopamine signaling are causal to vasculature dysfunction in Alzheimer’s
disease and can be targeted to mitigate vascular pathology. These studies will lead to the identification of
molecular pathways that drive neurovascular dysfunction in Alzheimer’s disease that may ultimately be useful
for preventing pathogenesis.

## Key facts

- **NIH application ID:** 10452103
- **Project number:** 1R21AG074163-01A1
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Melanie A Samuel
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $454,999
- **Award type:** 1
- **Project period:** 2022-05-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10452103

## Citation

> US National Institutes of Health, RePORTER application 10452103, Role of perictyte nanotubes in age-related neurovascular dysfunction (1R21AG074163-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10452103. Licensed CC0.

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