Quantitative Modelling of Amyloid-β Dynamics in Brain, CSF, and Plasma During Sleep and Wakefulness
- 1School of Physics, The University of Sydney, Camperdown, Australia
Abstract
Amyloid-beta (A{beta}) accumulation in the brain is linked to Alzheimer's disease. In healthy individuals, A{beta} rises during wakefulness and is cleared during sleep, yet the effects of sleep disturbances on the A{beta} dynamics are unclear. We developed a model, incorporating brain, cerebrospinal fluid (CSF), and plasma, to investigate the A{beta} dynamics along the sleep-wake cycles. The model reproduces the experimentally observed 24-hour A{beta}42 oscillations in CSF (660-760 pg/mL) and plasma (15-19 pg/mL) and predicts brain A{beta} dynamics. Indwelling lumbar catheter data show elevated CSF A{beta}42 levels on the second morning after a full night of sleep compared to first morning. The model predicts this increased level is due to repeated CSF sampling, which affects A{beta} levels through pressure-mediated changes in CSF, impaired sleep associated clearance, or their synergistic effect. These findings provide a framework for understanding A{beta} regulation, highlighting sleep's protective role and the need for non-invasive measurement approaches.
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BibTeX
@misc{sangeet2026quantitative,
title = {{Quantitative Modelling of Amyloid-β Dynamics in Brain, CSF, and Plasma During Sleep and Wakefulness}},
author = {S. Sangeet and C. L. Phillips and C. M. Hoyos and A. L. D'Rozario and B. P. Lucey and S. Postnova},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.07.749991},
url = {https://www.biorxiv.org/content/10.64898/2026.09.07.749991v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Quantitative Modelling of Amyloid-β Dynamics in Brain, CSF, and Plasma During Sleep and Wakefulness
AU - S. Sangeet
AU - C. L. Phillips
AU - C. M. Hoyos
AU - A. L. D'Rozario
AU - B. P. Lucey
AU - S. Postnova
PY - 2026
DA - 2026/09/07
PB - bioRxiv
DO - 10.64898/2026.09.07.749991
UR - https://www.biorxiv.org/content/10.64898/2026.09.07.749991v1
AB - Amyloid-beta (A{beta}) accumulation in the brain is linked to Alzheimer's disease. In healthy individuals, A{beta} rises during wakefulness and is cleared during sleep, yet the effects of sleep disturbances on the A{beta} dynamics are unclear. We developed a model, incorporating brain, cerebrospinal fluid (CSF), and plasma, to investigate the A{beta} dynamics along the sleep-wake cycles. The model reproduces the experimentally observed 24-hour A{beta}42 oscillations in CSF (660-760 pg/mL) and plasma (15-19 pg/mL) and predicts brain A{beta} dynamics. Indwelling lumbar catheter data show elevated CSF A{beta}42 levels on the second morning after a full night of sleep compared to first morning. The model predicts this increased level is due to repeated CSF sampling, which affects A{beta} levels through pressure-mediated changes in CSF, impaired sleep associated clearance, or their synergistic effect. These findings provide a framework for understanding A{beta} regulation, highlighting sleep's protective role and the need for non-invasive measurement approaches.
ER -