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Abstract Details

Altered CSF Flow Dynamics Measured by Low b-Value Diffusion MRI Associate with Amyloid Biomarkers in Alzheimer’s Disease
Aging, Dementia, and Behavioral Neurology
P4 - Poster Session 4 (8:00 AM-9:00 AM)
12-013
To investigate the relationship between cerebrospinal fluid (CSF) flow dynamics and amyloid biomarkers in Alzheimer’s disease (AD) using low-b-value-diffusion-MRI (dMRI)–derived pseudo-diffusivity (MΨ), a novel imaging marker of pseudorandom CSF flow.
Efficient CSF circulation is essential for clearing metabolic waste, including amyloid-β (Aβ) peptides, through pathways collectively described as the glymphatic system. Impairment of CSF flow has been implicated in amyloid accumulation and neurodegeneration. However, noninvasive quantification of CSF flow dynamics remains limited in clinical research. Low b-value dMRI offers a sensitive approach to detect subtle, multidirectional CSF motion, complementing conventional diffusion measures.
Participants were drawn from the Washington University Knight Alzheimer Disease Research Center cohort. Individuals with both low-b-dMRI and CSF biomarker data were included. Voxel-wise analyses (n=312) were performed on CSF MΨ maps generated using the CSF pseudo-diffusion spatial statistics (CΨSS) workflow and harmonized across seven Siemens 3 T scanners using ComBat. Region-of-interest (ROI) analysis (n=429) was performed using eleven regions from the CSF Waterways (CWW) atlas. Associations were tested between harmonized CSF MΨ values and CSF biomarkers across CWWs using general linear models adjusted for age, sex, and brain parenchyma fraction.
Increased CSF MΨ was associated with higher CSF Aβ40, with much weaker associations observed for Aβ42 and tau. Voxel-wise analysis showed significant positive correlations between CSF MΨ and CSF Aβ40, particularly within the Sylvian fissure and ventricular CSF spaces (FWE-p<0.05). ROI-analysis confirmed widespread positive associations between harmonized CSF MΨ and CSF Aβ40 across multiple CSF compartments, with the strongest effects in CWW-7 and CWW-8 (Sylvian fissure; FDR-p<0.05).

These findings highlight the role of regional CSF flow dynamics in modulating amyloid biomarkers. Given that Aβ40 preferentially deposits in cerebral vessels, altered CSF flow may contribute to vascular amyloid accumulation as seen in cerebral amyloid angiopathy, a process demonstrated in preclinical studies to be associated with glymphatic dysfunction.

 
Authors/Disclosures
Helia Hosseini, MD
PRESENTER 		Dr. Hosseini has nothing to disclose.
Aristeidis Sotiras, PhD Dr. Sotiras has stock in TheraPanacea. Dr. Sotiras has received personal compensation in the range of $500-$4,999 for serving as a Scientific Review Committee member with BrightFocus Foundation.
Brian Gordon, PhD Dr. Gordon has nothing to disclose.
Nelly C. Joseph-Mathurin, PhD The institution of Dr. Joseph-Mathurin has received research support from Alzheimer's Association. The institution of Dr. Joseph-Mathurin has received research support from National Institute on Aging. Dr. Joseph-Mathurin has received personal compensation in the range of $500-$4,999 for serving as a Facilitator AAIC Live Event with PeerView Institute For Medical 好色先生.
Chihiro Sato, PhD The institution of Dr. Sato has received research support from NIH. Dr. Sato has received intellectual property interests from a discovery or technology relating to health care.
Randall Bateman, MD (Washington Univ School of MedicinE) Dr. Bateman has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for C2N Diagnostics . Dr. Bateman has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for C2N Diagnostics . Dr. Bateman has received stock or an ownership interest from C2N Diagnostics. The institution of Dr. Bateman has received research support from Alzheimer's SILQ Research Fund/ Barnes Jewish Hospital Foundation . The institution of Dr. Bateman has received research support from National Institutes of Health- R21AG067559. The institution of Dr. Bateman has received research support from Centene Corporation. The institution of Dr. Bateman has received research support from Rainwater Charitable Foundation . The institution of Dr. Bateman has received research support from Cure Alzheimer's Fund. The institution of Dr. Bateman has received research support from Cure Alzheimer's Fund. The institution of Dr. Bateman has received research support from Anonymous Foundation. The institution of Dr. Bateman has received research support from Cure Alzheimer's Fund. The institution of Dr. Bateman has received research support from BrightFocus Foundation. The institution of Dr. Bateman has received research support from Assn for Frontotemporal Degeneration FTD Biomarkers Initiative. The institution of Dr. Bateman has received research support from Rainwater Foundation. The institution of Dr. Bateman has received research support from NIH- R01NS095773. The institution of Dr. Bateman has received research support from AbbVie/Biogen/Eli Lilly. The institution of Dr. Bateman has received research support from NIH/NINDS/NIA- RF1AG061900 (R56AG061900 & R01NS065667). The institution of Dr. Bateman has received research support from Eisai. The institution of Dr. Bateman has received research support from Good Ventures Foundation. The institution of Dr. Bateman has received research support from National Institutes of Health- R01 AG070941. The institution of Dr. Bateman has received research support from National Institutes of Health-. The institution of Dr. Bateman has received research support from National Institutes of Health. The institution of Dr. Bateman has received research support from NIH- P50AG005681-36. The institution of Dr. Bateman has received research support from NIH/NIA- U19AG032438. The institution of Dr. Bateman has received research support from Alzheimer's Association. The institution of Dr. Bateman has received research support from Pharma Consortium. The institution of Dr. Bateman has received research support from Eli Lilly . The institution of Dr. Bateman has received research support from NIH/NIA- NIH R01AG053267. The institution of Dr. Bateman has received research support from Administrative Supplement 01- NIH . The institution of Dr. Bateman has received research support from Administrative Supplement 02- NIH . The institution of Dr. Bateman has received research support from NIH- 1U01AG059798. The institution of Dr. Bateman has received research support from NIH- R01AG068319. The institution of Dr. Bateman has received research support from Alzheimer's Association. The institution of Dr. Bateman has received research support from Alzheimer's Association. The institution of Dr. Bateman has received research support from Alzheimer's Association. The institution of Dr. Bateman has received research support from Roche. The institution of Dr. Bateman has received research support from NIH/NIA- R01AG046179. The institution of Dr. Bateman has received research support from GHR; Anonymous Foundation. The institution of Dr. Bateman has received research support from NIH/NIA- 1U01AG042791, 1U01AG042791. The institution of Dr. Bateman has received research support from Alzheimer's Association. The institution of Dr. Bateman has received research support from NIH/State Government- 5U19AG010483. Dr. Bateman has received intellectual property interests from a discovery or technology relating to health care.
Tammie Benzinger (Washington University) Tammie Benzinger has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Tammie Benzinger has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Tammie Benzinger has received personal compensation in the range of $0-$499 for serving as a Consultant for Sora Neuroscience. Tammie Benzinger has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eli Lilly. Tammie Benzinger has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eisai. Tammie Benzinger has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Tammie Benzinger has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Johnson & Johnson. Tammie Benzinger has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol, Myers Squibb. Tammie Benzinger has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for PeerView. Tammie Benzinger has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Medscape. The institution of Tammie Benzinger has received research support from Siemens. The institution of Tammie Benzinger has received research support from Hyperfine. Tammie Benzinger has a non-compensated relationship as a Consultant with Siemens that is relevant to AAN interests or activities. Tammie Benzinger has a non-compensated relationship as a Consultant with Eisai that is relevant to AAN interests or activities.
Arash Nazeri, MD Dr. Nazeri has nothing to disclose.