# The roles of pericyte-derived laminin in neurovascular function and neurodegeneration

> **NIH NIH RF1** · UNIVERSITY OF SOUTH FLORIDA · 2021 · $1,811,097

## Abstract

Project Summary/Abstract
The long-term objective of this application is to understand whether the basement membrane (BM), the
non-cellular component of the neurovascular unit, is involved in the pathogenesis of Alzheimer’s
disease and can be targeted to treat Alzheimer’s disease and Alzheimer’s disease-related dementias.
This is consistent with the mission of NIA. This proposal aims to investigate the biological functions of
pericytic laminin in: (1) neurovascular function, including blood brain barrier (BBB) integrity, cerebral
blood flow (CBF) and brain influx/efflux function, and (2) neuronal survival/function. In Aim 1, the
function of pericytic laminin in BBB integrity will be investigated. First, whether and to what extent loss
of pericytic laminin affects BBB integrity will be investigated using FITC-Dextrans of various molecular
weights (Aim 1A). Next, the molecular mechanism underlying loss of pericytic laminin-induced BBB
breakdown will be investigated, with a focus on changes in paracellular and transcellular transport in
endothelial cells (Aim 1B). Furthermore, the receptors that mediate pericytic laminin’s effect in
endothelial cells will be identified and examined (Aim 1C). In Aim 2, the function of pericytic laminin in
CBF will be investigated. First, how loss of pericytic laminin affects CBF will be investigated using
quantitative autoradiography and two-photon imaging (Aim 2A). Next, whether the reduced CBF is
caused by pericyte loss/degeneration will be investigated in vitro and in vivo (Aim 2B). Furthermore, the
receptors that mediate pericytic laminin’s effect in pericytes will be identified and examined (Aim 2C). In
Aim 3, the role of pericytic laminin in brain influx/efflux function will be investigated. First, whether and
how loss of pericytic laminin affects brain influx/efflux function will be investigated by influx/efflux
assays using various fluorescently labeled macromolecules (Aim 3A). Next, whether the impaired
influx/efflux function is due to BM damage and how loss of pericytic laminin affects BM
composition/structure will be explored (Aim 3B). In Aim 4, the function of pericytic laminin in neuronal
injury/neurodegeneration will be investigated. In this aim, whether loss of pericytic laminin leads to
neuronal injury/neurodegeneration will be investigated at biochemical, structural, and functional levels.
In addition, the age at which neuronal injury/neurodegeneration occurs will be determined and
compared to that at which neurovascular dysfunction occurs. Successful completion of this study will
elucidate the fundamental roles of pericytic laminin in neurovascular function and neuronal
survival/function, and identify novel molecular targets with therapeutic potential in Alzheimer’s disease
and Alzheimer’s disease-related dementias. In addition, this proposal may also lead to the generation
of an innovative mouse model for neurodegeneration and open doors for new research.

## Key facts

- **NIH application ID:** 10296497
- **Project number:** 1RF1AG065345-01A1
- **Recipient organization:** UNIVERSITY OF SOUTH FLORIDA
- **Principal Investigator:** Yao Yao
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,811,097
- **Award type:** 1
- **Project period:** 2021-09-30 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10296497

## Citation

> US National Institutes of Health, RePORTER application 10296497, The roles of pericyte-derived laminin in neurovascular function and neurodegeneration (1RF1AG065345-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10296497. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*