Objective:

To investigate the relationship between regional CSF flow and CSF amyloid-β (Aβ) levels.

Background:

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.

Design/Methods:

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.

Results:

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.

Conclusions:

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.