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Regional Cerebrospinal Fluid Motility as a Key Determinant of Soluble Amyloid-β Levels and Kinetics
Nazeri A, Hosseini H, Sotiras A, Sato C, Elbert D, Yang B, Joseph-Mathurin N, Ovod V et al.. Research Square, 2026-08-03
Topic: Plasma and spinal-fluid biomarkers
Alzheimer’s disease and cerebral amyloid angiopathy are characterized by the accumulation of amyloid-β (Aβ) species, yet the human fluid-physiological mechanisms that regulate soluble Aβ transport and clearance remain poorly understood. Aβ40, the dominant vascular Aβ species, remains relatively soluble and accumulates preferentially along vascular basement membranes, making it especially relevant to CSF-mediated clearance pathways. Here, we used non-invasive low b-value diffusion MRI to quantify regional effective CSF motility in a large multimodal cohort from the Knight Alzheimer Disease Research Center, including participants with CSF biomarkers (n = 502), plasma biomarkers (n = 459), amyloid PET imaging (n = 270), and stable isotope labeling kinetics data (n = 40). Effective CSF motility was quantified as mean pseudo-diffusivity (Mψ) and mapped using CSF pseudo-diffusion spatial statistics with a data-driven CSF Waterways atlas. Higher regional CSF motility was consistently associated with higher CSF Aβ40 concentrations, with convergent voxel-wise and region-of-interest effects across ventricular and extra-axial CSF compartments that were most prominent in peri-Sylvian CSF pathways. Across regions, CSF motility measures collectively explained approximately 18% of the variance in CSF Aβ40. A weaker, spatially restricted association was also observed with plasma Aβ40. In contrast, associations with CSF Aβ42 were smaller, anatomically limited, and further attenuated among participants with amyloid deposition on PET. In participants with stable isotope labeling kinetics, higher transventricular and cranio-cervical CSF motility was associated with earlier peak enrichment of labeled Aβ40 and Aβ42, while greater lateral ventricular motility was associated with faster fractional turnover of both peptides. Collectively, these findings identify effective CSF motility as an important physiological determinant of soluble Aβ levels in plasma and CSF, linking regional CSF dynamics to in vivo Aβ transport and turnover, with potential relevance to cerebral amyloid angiopathy and Alzheimer’s disease.
Key findings
- Higher regional CSF motility was consistently associated with higher CSF Aβ40 concentrations, with convergent voxel-wise and region-of-interest effects across ventricular and extra-axial CSF compartments that were most prominent in peri-Sylvian CSF pathways.
- In participants with stable isotope labeling kinetics, higher transventricular and cranio-cervical CSF motility was associated with earlier peak enrichment of labeled Aβ40 and Aβ42, while greater lateral ventricular motility was associated with faster fractional turnover of both peptides.
- Collectively, these findings identify effective CSF motility as an important physiological determinant of soluble Aβ levels in plasma and CSF, linking regional CSF dynamics to in vivo Aβ transport and turnover, with potential relevance to cerebral amyloid angiopathy and Alzheimer’s disease.
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Study details
- Participants502
- Evidence strengthModerate
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 32 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, effect reported 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 20 of the 62 points we could judge it on, which is 32 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (Research Square) |
| 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 | 3 / 5 | Rated “moderate” 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 | 2 / 4 | 502 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| 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 | 20 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 20 of the 62 points we could judge it on is 32 out of 100. |
| Total | 32 / 100 | Capped to 16 because this is not a peer-reviewed article. |
What each of these 20 components measures, and what this score is not →
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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. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Nazeri, A., Hosseini, H., Sotiras, A., Sato, C., Elbert, D., Yang, B., et al. (2026). Regional Cerebrospinal Fluid Motility as a Key Determinant of Soluble Amyloid-β Levels and Kinetics. Research Square. https://doi.org/10.21203/rs.3.rs-10530209/v1
Vancouver
Nazeri A, Hosseini H, Sotiras A, Sato C, Elbert D, Yang B, et al. Regional Cerebrospinal Fluid Motility as a Key Determinant of Soluble Amyloid-β Levels and Kinetics. Research Square. 2026. doi:10.21203/rs.3.rs-10530209/v1.
BibTeX
@article{nazeri2026-89aedc92,
author = {Nazeri, A. and Hosseini, H. and Sotiras, A. and Sato, C. and Elbert, D. and Yang, B. and Joseph-Mathurin, N. and Ovod, V. and others},
title = {{Regional Cerebrospinal Fluid Motility as a Key Determinant of Soluble Amyloid-β Levels and Kinetics}},
journal = {Research Square},
year = {2026},
doi = {10.21203/rs.3.rs-10530209/v1},
url = {https://doi.org/10.21203/rs.3.rs-10530209/v1}
}
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