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Quantitative Modelling of Amyloid-β Dynamics in Brain, CSF, and Plasma During Sleep and Wakefulness
Sangeet S, Phillips CL, Hoyos CM, D’Rozario AL, Lucey BP, Postnova S.. bioRxiv, 2026-09-14
Topic: Plasma and spinal-fluid biomarkers
Amyloid-beta (Aβ) accumulation in the brain is linked to Alzheimer’s disease. In healthy individuals, Aβ rises during wakefulness and is cleared during sleep, yet the effects of sleep disturbances on the Aβ dynamics are unclear. We developed a model, incorporating brain, cerebrospinal fluid (CSF), and plasma, to investigate the Aβ dynamics along the sleep-wake cycles. The model reproduces the experimentally observed 24-hour Aβ42 oscillations in CSF (660–760 pgml -1 ) and plasma (15–19 pgml -1 ) and predicts brain Aβ dynamics. Indwelling lumbar catheter data show elevated CSF Aβ42 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 Aβ levels through pressure-mediated changes in CSF, impaired sleep-associated clearance, or their synergistic effect. These findings provide a framework for understanding Aβ regulation, highlighting sleep’s protective role and the need for non-invasive measurement approaches. Highlights A quantitative three-compartment model captures 24-hour amyloid-beta dynamics across brain, CSF, and plasma during sleep-wake cycles in healthy individuals. The model reproduces normal sleep-wake activity of amyloid-beta in CSF and plasma, consistent with healthy physiological dynamics. Model predicts brain amyloid-beta concentrations, providing insights into dynamics experimentally challenging to measure. Experimental datasets with repeated lumbar punctures show day-to-day CSF amyloid beta accumulation, deviating from stable dynamics expected under healthy homeostasis. The model predicts lumbar punctures alter CSF amyloid beta levels through pressure-mediated changes in CSF, sleep-dependent glymphatic clearance, or both.
Key findings
- Indwelling lumbar catheter data show elevated CSF Aβ42 levels on the second morning after a full night of sleep compared to first morning.
- These findings provide a framework for understanding Aβ regulation, highlighting sleep’s protective role and the need for non-invasive measurement approaches.
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Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 21 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 13 of the 62 points we could judge it on, which is 21 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (bioRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 13 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 13 of the 62 points we could judge it on is 21 out of 100. |
| Total | 21 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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APA 7th
Sangeet, S., Phillips, C. L., Hoyos, C. M., D’Rozario, A. L., Lucey, B. P., & Postnova, S. (2026). Quantitative Modelling of Amyloid-β Dynamics in Brain, CSF, and Plasma During Sleep and Wakefulness. bioRxiv. https://doi.org/10.64898/2026.09.07.749991
Vancouver
Sangeet S, Phillips CL, Hoyos CM, D’Rozario AL, Lucey BP, Postnova S. Quantitative Modelling of Amyloid-β Dynamics in Brain, CSF, and Plasma During Sleep and Wakefulness. bioRxiv. 2026. doi:10.64898/2026.09.07.749991.
BibTeX
@article{sangeet2026-ef7d1dde,
author = {Sangeet, S. and Phillips, C. L. and Hoyos, C. M. and D’Rozario, A. L. and Lucey, B. P. and Postnova, S.},
title = {{Quantitative Modelling of Amyloid-β Dynamics in Brain, CSF, and Plasma During Sleep and Wakefulness}},
journal = {bioRxiv},
year = {2026},
doi = {10.64898/2026.09.07.749991},
url = {https://doi.org/10.64898/2026.09.07.749991}
}