# Understanding CSF Clearance in Aging and Alzheimer’s Brain Through Dynamic Sodium MRI - Resubmission - 1

> **NIH NIH RF1** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2021 · $2,336,665

## Abstract

ABSTRACT
Disruption of cerebrospinal fluid (CSF) clearance pathway (glymphatic system) might contribute to development
of Alzheimer's disease (AD), which is characterized by excessive deposition of toxic soluble amyloid beta (A-
beta) proteins in the brain. Recent studies of mice demonstrated that impairment of the CSF clearance pathway
led to a 70% reduction in A-beta clearance, while sleep-induced enhancement of CSF flow increased A-beta
clearance by 100%. It is unclear whether or not these impairment and enhancement effects exist in humans and
how they change with aging. Technical limitations of noninvasive approaches hinder adequate study of CSF
clearance in humans. Here we propose two new techniques to determine whether CSF clearance is enhanced
during sleep, degenerated in normal aging, and disrupted in AD. Instead of studying perivascular space, this
project investigates the production (at choroid plexus), bulk flow (in parenchyma), and drainage (at arachnoid
villi) of CSF in the brain simultaneously. The overarching goal is to understand the changes in CSF clearance in
normal aging and in AD. The proposed techniques include 1) dynamic sodium (23Na) MRI that quantifies velocity
of CSF bulk flow in brain parenchyma and 2) ultrashort echo time (UTE) proton (1H) MRI that uses UTE-T2*
value to quantify calcification of choroid plexus and assess deficiency of CSF production and uses high resolution
(0.22 mm) to visualize trabecular structures in arachnoid villi and evaluate resistance of CSF drainage. We aim
to determine: 1) how age affects CSF production, bulk flow, and drainage in the normal brain; 2) the impact of
sleep on CSF clearance in the normal aging brain; and 3) whether CSF clearance is disrupted in AD patients.
This work will generate highly-desired valuable knowledge about the degeneration of CSF clearance in normal
aging and disruption in AD, which will help design and determine effective interventions for and strategies to
prevention of AD development.

## Key facts

- **NIH application ID:** 10126415
- **Project number:** 1RF1AG067502-01A1
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Yongxian Qian
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $2,336,665
- **Award type:** 1
- **Project period:** 2021-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10126415

## Citation

> US National Institutes of Health, RePORTER application 10126415, Understanding CSF Clearance in Aging and Alzheimer’s Brain Through Dynamic Sodium MRI - Resubmission - 1 (1RF1AG067502-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10126415. Licensed CC0.

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