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Updated: Jul 5, 2026
A Technique for Serial Collection of Cerebrospinal Fluid from the Cisterna Magna in Mouse
Published on: November 10, 2008
The coupling of global brain activity and cerebrospinal fluid flow as a potential predictive marker of brain
Yuya Tanaka1, Koji Kamagata2, Yuya Saito2
1Department of Radiology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113-8421, Japan; Department of Radiology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan.
Background:
Impaired cerebrospinal fluid (CSF) clearance is thought to contribute to amyloid-β (Aβ) accumulation in Alzheimer's disease (AD). Global brain activity-CSF flow coupling (gBOLD-CSF coupling), measured through resting-state functional MRI, reflects CSF clearance capacity. A higher coupling value indicates weaker coupling. Its potential as a predictive marker for Aβ accumulation remains unclear.
Objectives:
This study aims to determine whether weaker gBOLD-CSF coupling precedes Aβ accumulation in cognitively normal, Aβ-negative individuals and to explore its predictive potential for amyloid conversion.
Design:
A longitudinal observational study using Alzheimer's Disease Neuroimaging Initiative (ADNI) data.
Setting:
Data from ADNI-participating sites.
Participants:
16 cognitively normal participants, initially Aβ-negative: seven fast-converters (transitioned to Aβ-positive within two years) and nine slow-converters (remained Aβ-negative for at least two years).
Measurements:
gBOLD-CSF coupling was calculated as the Pearson correlation coefficient between global Blood-Oxygen-Level-Dependent (BOLD) and CSF inflow signals. Group differences in gBOLD-CSF coupling were analyzed, along with partial correlation analyses between gBOLD-CSF coupling and annual changes in Aβ biomarkers and cognitive scores.
Results:
Fast-converters showed significantly higher gBOLD-CSF coupling values, indicating weaker coupling (Cohen's d = 1.76, p = 0.012). Coupling values positively correlated with annual changes in Aβ-PET SUVR (r = 0.594, p = 0.054) and negatively with MoCA scores (r = -0.654, p = 0.021).
Conclusion:
Weaker gBOLD-CSF coupling precedes brain Aβ accumulation, indicating its potential as a predictive marker for amyloid conversion. Future studies should refine clinical thresholds for early intervention strategies in AD prevention.
