Fluctuations of CSF amyloid-β levels: Implications for a diagnostic and therapeutic biomarker

OBJECTIVE: To investigate the stability and time course of human CSF amyloid-β (Aβ) levels over hours. METHODS: Fifteen nondemented participants had CSF sampled hourly for up to 36 hours via indwelling lumbar catheter. CSF Aβ1-x, Aβ1-40, and Aβ1-42 were measured by ELISA in each hourly CSF sample. RESULTS: Significant variation in Aβ levels of 1.5- to fourfold was detected over 36 hours of serially sampling in individual subjects. Aβ40, Aβ42, and Aβ1-X are highly correlated over time indicating that similar processes likely regulate the level of these species. On average, the fluctuations of Aβ levels appear to be time of day or activity dependent. CONCLUSION: Diagnostic and therapeutic trials that measure Aβ should control for the time of CSF sampling to minimize variability.