# Mapping the perivascular reticular network in health, aging, and AD

> **NIH NIH RF1** · RUSH UNIVERSITY MEDICAL CENTER · 2023 · $1,246,362

## Abstract

PROJECT SUMMARY/ABSTRACT
Perivascular space (PVS) pia is a unique tissue composite within the mammalian nervous system and is
traversed by cerebrospinal fluid (CSF) during CSF-interstitial fluid exchange. PVS are known to become more
complex with aging. Accumulating evidence suggests that PVS subserve specialized roles in glymphatic-
lymphatic transport and may be a critical factor in brain resilience and diseases, including Alzheimer’s disease.
In spite of this, the basic structure of brain pia is minimally investigated across species. Historically, pia has been
perceived to play passive roles as an ultrafine membrane that restricts fluid movement at the brain surface.
Substantial gaps in knowledge remain regarding the specific morphology and constituents of this meningeal
layer and its associations with disease, due in large part to lack of systematic and high-resolution microscopic
analyses. To advance the field, better characterization of pia structure is needed. In this project, high-resolution
microscopy techniques will be used to elucidate the morphology of human pia mater and its morphological and
compositional changes with aging. Pial anatomy will be mapped using immunohistochemical techniques and its
properties will be correlated with established neuropathological and neurological measures of disease. For this
work, we will leverage a rich resource of clinical and pathologic material available from the Rush Religious Orders
Study and Memory and Aging Project (ROSMAP) and will collect and analyze novel data pertaining to the unique
structure of PVS pia. The hypothesis is that PVS pia functions as a critical neuroimmune tissue and that pial
senescence is associated with Alzheimer’s disease (AD). In Aim 1, we will examine the associations of pial
morphology with intracranial beta-amyloid (βA) accumulation and pathology of AD. In Aim 2, we will examine the
associations of pial morphology with cognitive decline and resilience. In Aim 3, we will explore the associations
of pial morphology with PVS and brain inflammation. In each aim, we will investigate how relationships differ by
age, sex, and comorbid diseases. Overall, these studies have the potential to uncover new knowledge regarding
the function of pia mater in aging and AD as well as novel insights into its heterogeneity in aging. The proposed
investigations will advance the field and may reveal mechanistic, diagnostic and prognostic factors for AD while
laying a framework for studying this meningeal layer in the setting of other age-related neurological diseases.

## Key facts

- **NIH application ID:** 10739104
- **Project number:** 1RF1AG083765-01
- **Recipient organization:** RUSH UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Rupal I. Mehta
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $1,246,362
- **Award type:** 1
- **Project period:** 2023-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10739104

## Citation

> US National Institutes of Health, RePORTER application 10739104, Mapping the perivascular reticular network in health, aging, and AD (1RF1AG083765-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10739104. Licensed CC0.

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