Effects of Age and Amyloid Deposition on Aβ Dynamics in the Human Central Nervous System

Background: The amyloid hypothesis predicts that increased production or decreased clearance of beta-amyloid (A beta) leads to amyloidosis, which ultimately culminates in Alzheimer disease (AD). Objective: To investigate whether dynamic changes in A beta levels in the human central nervous system may be altered by aging or by the pathology of AD and thus contribute to the risk of AD. Design: Repeated-measures case-control study. Setting: Washington University School of Medicine in St Louis, Missouri. Participants: Participants with amyloid deposition, participants without amyloid deposition, and younger normal control participants. Main Outcome Measures: In this study, hourly cerebrospinal fluid (CSF) A beta concentrations were compared with age, status of amyloid deposition, electroencephalography, and video recording data. Results: Linear increases were observed over time in the A beta levels in CSF samples obtained from the younger normal control participants and the older participants without amyloid deposition, but not from the older participants with amyloid deposition. Significant circadian patterns were observed in the A beta levels in CSF samples obtained from the younger control participants; however, circadian amplitudes decreased in both older participants without amyloid deposition and older participants with amyloid deposition. A beta diurnal concentrations were correlated with the amount of sleep but not with the various activities that the participants participated in while awake. Conclusions: A reduction in the linear increase in the A beta levels in CSF samples that is associated with amyloid deposition and a decreased CSF A beta diurnal pattern associated with increasing age disrupt the normal physiology of A beta dynamics and may contribute to AD.