# CSF Clearance in Sporadic Alzheimer's Disease

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2021 · $809,831

## Abstract

PROJECT SUMMARY / ABSTRACT
CSF drainage pathology, a potential new Alzheimer's disease (AD) therapeutic target, has been hypothesized
as impaired in AD and demonstrated in AD models. There is no non-invasive technique to measure the brain
CSF clearance (BCC) in humans. Low molecular weight PET tracers such as 18F-MK6240, 18F-THK5351 and
11C-PiB, like other ISF solutes, rapidly enter and clear the brain. They can freely pass the BBB, distribute into
brain and ISF spaces, and move into the ventricular CSF through the glymphatic system. We have developed
a method to use radiotracer clearance from brain as a biomarker for glymphatic clearance. Our recent paper
and preliminary dynamic PET studies demonstrate that radiotracer distribution in ventricular CSF from 35 to 60
minutes (vCSF-AUC) is a valuable marker to estimate BCC. Our preliminary data demonstrate that after
controlling for blood tracer levels, vCSF-AUC are highly reproducible within subjects across tau and amyloid
PET tracers and achieve 90% accuracy for group separation between normal and impaired subjects. BCC
correlated inversely with brain amyloid deposition, cognitive performance and cortical thickness even after
controlling for confounds. These observations justify our proposed 2-year longitudinal study to evaluate the
vCSF-AUC as a global predictor of Aβ deposition. Secondarily, we will examine the clearance deficit in early
stages of AD and association with features of neurodegeneration (atrophy and cognitive function). This study is
a novel attempt to improve our understanding of a proposed mechanism for AD. We anticipate this project will
facilitate research into the development of risk factors, epidemiology, prevention and treatment of AD.

## Key facts

- **NIH application ID:** 9993210
- **Project number:** 5R01AG057848-03
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Yi Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $809,831
- **Award type:** 5
- **Project period:** 2019-08-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9993210

## Citation

> US National Institutes of Health, RePORTER application 9993210, CSF Clearance in Sporadic Alzheimer's Disease (5R01AG057848-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9993210. Licensed CC0.

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