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Brain-wide Cerebrospinal Fluid Recirculation Collapse in Alzheimer’s Disease
Choi M, Kim K, Kim I, Jung MK, Kim D.. bioRxiv, 2026-10-04
Topic: Inflammation, microglia and astrocytes
Cerebrospinal fluid (CSF) flow and the glymphatic system are essential for maintaining brain homeostasis, yet the precise mechanisms driving their profound failure in Alzheimer’s disease (AD) remain largely elusive. Here, we reveal that macroscopic CSF propagates dorsally via the perivascular spaces (PAS) of major ventral arteries—the Circle of Willis (CW), middle cerebral artery (MCA), and olfactory artery (OlfA)—which undergo severe structural degradation in an AD mouse model. High-resolution imaging of the dorsal cortex demonstrates that this structural collapse induces a severe influx blockade; in AD, CSF tracers form massive aggregates within the PAS, physically decoupling the gliovascular interface, while tracers entering the parenchyma are pathologically sequestered by amyloid plaques. Furthermore, we identify an active, cholesterol-mediated clearance mechanism responding to exogenous CSF tracer infiltration. While healthy brains rapidly synthesize and efficiently clear this cholesterol via vascular efflux within 120 minutes, the AD model exhibits blunted cholesterol mobilization and a complete failure of capillary efflux. This terminal bottleneck forces uncleared cholesterol to retrogradely accumulate into pathological aggregates within perivascular pericytes and neuronal somata. Collectively, our findings demonstrate that AD dismantles the entire CSF recirculation loop—from macroscopic ventral entry to terminal microvascular efflux—highlighting pericytic and neuronal lipidosis as fundamental drivers of brain fluid stagnation.
Key findings
- Collectively, our findings demonstrate that AD dismantles the entire CSF recirculation loop—from macroscopic ventral entry to terminal microvascular efflux—highlighting pericytic and neuronal lipidosis as fundamental drivers of brain fluid stagnation.
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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Preprint — not yet peer-reviewed.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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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Choi, M., Kim, K., Kim, I., Jung, M. K., & Kim, D. (2026). Brain-wide Cerebrospinal Fluid Recirculation Collapse in Alzheimer’s Disease. bioRxiv. https://doi.org/10.64898/2026.10.01.755971
Vancouver
Choi M, Kim K, Kim I, Jung MK, Kim D. Brain-wide Cerebrospinal Fluid Recirculation Collapse in Alzheimer’s Disease. bioRxiv. 2026. doi:10.64898/2026.10.01.755971.
BibTeX
@article{choi2026-a92521b4,
author = {Choi, M. and Kim, K. and Kim, I. and Jung, M. K. and Kim, D.},
title = {{Brain-wide Cerebrospinal Fluid Recirculation Collapse in Alzheimer’s Disease}},
journal = {bioRxiv},
year = {2026},
doi = {10.64898/2026.10.01.755971},
url = {https://doi.org/10.64898/2026.10.01.755971}
}
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