Quantitative Modelling of Amyloid-β Dynamics in Brain, CSF, and Plasma During Sleep and Wakefulness

Amyloid-beta (A{beta}) accumulation in the brain is associated with Alzheimer's disease. Typically, A{beta} levels surge during wakefulness and decrease during sleep. However, the impact of sleep disturbances on A{beta} dynamics remains uncertain. To investigate this, researchers created a model considering brain, cerebrospinal fluid (CSF), and plasma.

The model accurately reflected the 24-hour A{beta}42 oscillations observed in CSF (660-760 pg/mL) and plasma (15-19 pg/mL). Additionally, it forecasted brain A{beta} dynamics. Data from indwelling lumbar catheters revealed higher CSF A{beta}42 levels in the second morning after a full night of sleep compared to the first morning.

The model suggests this elevated level is likely due to repeated CSF sampling, which alters A{beta} levels through pressure-mediated changes in CSF, impaired sleep-associated clearance, or a combination of both factors. These insights provide a framework for understanding A{beta} regulation, emphasizing sleep's protective role and the necessity for non-invasive measurement methods.