Water exchange rate across the blood-brain barrier is associated with CSF amyloid-β 42 in healthy older adults

Introduction: We tested if water exchange across the blood-brain barrier (BBB), estimated with a noninvasive magnetic resonance imaging (MRI) technique, is associated with cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) and neuropsychological function. Methods: Forty cognitively normal older adults (67–86 years old) were scanned with diffusion-prepared, arterial spin labeling (DP-ASL), which estimates water exchange rate across the BBB (k_w). Participants also underwent CSF draw and neuropsychological testing. Multiple linear regression models were run with k_w as a predictor of CSF concentrations and neuropsychological scores. Results: In multiple brain regions, BBB k_w was positively associated with CSF amyloid beta (Aβ)42 concentration levels. BBB k_w was only moderately associated with neuropsychological performance. Discussion: Our results suggest that low water exchange rate across the BBB is associated with low CSF Aβ42 concentration. These findings suggest that k_w may be a promising noninvasive indicator of BBB Aβ clearance functions, a possibility which should be further tested in future research.