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Abstract Details

The Interplay Between CSF Circulation and Amyloid-Beta Levels
Aging, Dementia, and Behavioral Neurology
P1 - Poster Session 1 (11:45 AM-12:45 PM)
3-009
To investigate the relationship between regional CSF flow and CSF amyloid-β (Aβ) levels.
The accumulation of Aβ is a hallmark of Alzheimer’s disease (AD) and cerebral amyloid angiopathy. The cerebrospinal fluid (CSF) plays a critical role in clearing Aβ peptides from the brain, particularly as alternative clearance pathways diminish with age.
Diffusion-weighted MRI at low b-values (low-b dMRI) enables whole-brain mapping of CSF effective motility estimated with mean pseudo-diffusivity (MΨ). A neuroimaging cohort from the Washington University Knight ADRC (n=123; 18 mild cognitive impairment; 2 AD; age: 69±8.7 years) underwent low-b dMRI acquired on a 3T MRI system. Whole-brain voxel-wise analysis was performed to assess the relationship between CSF MΨ and the CSF Aβ biomarkers (Aβ40, Aβ42, Aβ42/Aβ40-ratio), using CSF pseudo-diffusion spatial statistics (CΨSS).  Region-of-interest (ROI) analysis was performed using eleven regions from the CSF water ways (CWW) atlas. All statistical tests were adjusted for age and sex.
Whole-brain voxel-wise analysis revealed that higher CSF Aβ40 levels were associated with higher CSF MΨ within the lateral ventricles and right Sylvian fissure (family-wise error-corrected, p<0.05). No significant associations were found for Aβ42 and Aβ42/Aβ40-ratio. ROI analyses across eleven CWWs showed that higher CSF MΨ in six regions—the lateral ventricles, craniocervical junction, prepontine cistern, perimesencephalic cisterns, and Sylvian fissures—was associated with elevated CSF Aβ40 levels (FDR-corrected, p<0.05). Positive associations were identified between CSF MΨ in 2 CWWs and CSF Aβ42 (FDR-corrected, p<0.05). No significant associations were found between CSF MΨ and the Aβ42/Aβ40-ratio in the ROI analysis.
The positive correlation between CSF Aβ levels and CSF flow suggests that increased CSF dynamics may enhance Aβ peptide clearance. This study also highlights the role of regional CSF flow patterns in influencing CSF Aβ levels as biomarkers, suggesting that interindividual differences in intracranial CSF flow may contribute to unaccounted variability in CSF Aβ measurements.
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.