# Measuring impairment of extracellular solute transport in Alzheimer's disease

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $444,125

## Abstract

Project summary/abstract
The extracellular space (ECS) of the brain consists of a highly interconnected network of narrow tunnel and
sheet-like structures with width of 10-80 nm. Perivascular spaces surrounding blood vessels connect with the
ECS and act as conduits for transport of solutes throughout the parenchyma and to the CSF at the surface of
the brain. Nutrient delivery to tissues, clearance of toxic protein aggregates and therapeutic delivery to targets
require transport through the ECS and considerable uncertainty exists regarding the rates and mechanisms of
transport in vivo. Specifically, neither the rate, direction or regulation of solute transport in the perivascular
spaces are well understood. Recently, we demonstrated that multiphoton fluorescence recovery after
photobleaching (MP-FRAP) of exogenous fluorophores introduced into the ECS can be used to directly
measure solute transport rates deep within the brain parenchyma in vivo. Experiments to be performed here
will adapt this technique to measure the rates and direction of perivascular solute transport in mouse brain and
thereby resolve basic questions regarding the physiology of these spaces. In Alzheimer’s disease (AD),
amyloid plaques form in the parenchyma and around blood vessels, causing extensive changes in structure
and function of the surrounding glia. The consequences of these changes for transport of solutes in the
perivascular space remain largely unknown and we will utilize AD model mice to determine if deposition of Aβ
around vessels impairs perivascular solute movement. It is hoped that these experiments will lead to a
quantitative and well substantiated understanding of perivascular extracellular transport in the brain, and
suggest approaches for enhancing endogenous clearance mechanisms and improving therapeutic delivery.

## Key facts

- **NIH application ID:** 10511544
- **Project number:** 1R21AG078873-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Alexander James Smith
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $444,125
- **Award type:** 1
- **Project period:** 2022-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10511544

## Citation

> US National Institutes of Health, RePORTER application 10511544, Measuring impairment of extracellular solute transport in Alzheimer's disease (1R21AG078873-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10511544. Licensed CC0.

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