# Quantitative imaging of choroid plexus function and neurofluid circulation in Alzheimer's Disease Related Dementia

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2024 · $580,371

## Abstract

PROJECT SUMMARY
The goal of this work is to refine neuroimaging methods to enable quantitation of choroid plexus (ChP) anatomy
and function non-invasively in vivo, and subsequently to use these methods to test fundamental hypotheses
regarding ChP activity, cerebrospinal fluid (CSF) flow, and anatomical and protein markers of molecular
clearance dysfunction in patients with Alzheimer’s Disease Related Dementias (ADRDs). The premise for this
work is based on the known role of the ChP complexes for CSF production, and the recent link between
bulk and perivascular CSF flow dysfunction in neurodegenerative disorders, yet a lack of robust
methods for quantifying these pathways in humans. We have shown that arterial spin labeling (ASL)
magnetic resonance imaging (MRI) methods and deep learning algorithms can be re-parameterized to enable
reproducible estimates of ChP perfusion (ml/100g/min) at high spatial resolution and accurate automated
localization, respectively: in preliminary data from 139 volunteers, we have (i) demonstrated abilities to
obtain reproducible ChP perfusion estimates in healthy adults (n=10); (ii) observed that improvements
in vascular health reduce ChP activity (n=23) and progressive intracranial vasculopathy increases ChP
perfusion (n=75); and (iii) report here that in older adults with ADRDs, ChP is elevated relative to age-
matched adults without dementia (n=31). These data highlight the possibility of evaluating ChP function in
vivo in neurodegenerative and cerebrovascular disease. However, extant methods require refinement to improve
ChP localization and quantitative accuracy, including an expanded knowledge of ChP physiology and how ChP
activity relates to anatomical markers of molecular clearance and symptomatology. Here, we propose to address
these gaps in our understanding. In Aim (1), we will perform systematic measurements of ChP MRI relaxation
times and circulatory dynamics; findings will improve ChP perfusion accuracy beyond current approaches that
utilize convenience calibration values from other tissues. In Aim (2), we will extend prior studies demonstrating
circadian variation in CSF production to quantify diurnal variation in ChP perfusion during sleep and wakefulness;
results will serve as a necessary prerequisite for future studies that utilize ChP function as a surrogate or
complement to glymphatic or CSF flow dysfunction. In Aim (3), we will quantify ChP perfusion in participants
with ADRD in sequence with bulk CSF flow velocity through the cerebral aqueduct, parasagittal dural volume,
and proteinopathy. Data will be used to test fundamental hypotheses regarding the relevance of ChP activity and
impaired trans-molecular passage in the setting of normal and heightened amyloid burden and clinical dementia.
Findings will provide the first data on how ChP activity, quantified non-invasively in vivo from high
spatial resolution perfusion MRI, reflects variation in traditional or novel fluid efflux. Successful
comple...

## Key facts

- **NIH application ID:** 10914898
- **Project number:** 5R01AG083159-02
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Manus J Donahue
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $580,371
- **Award type:** 5
- **Project period:** 2023-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10914898

## Citation

> US National Institutes of Health, RePORTER application 10914898, Quantitative imaging of choroid plexus function and neurofluid circulation in Alzheimer's Disease Related Dementia (5R01AG083159-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10914898. Licensed CC0.

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