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Choroid plexus free‐water correlates with glymphatic function in Alzheimer's disease
Xiaomeng Xu, Xinyuan Yang, Junfang Zhang, Yan Wang, Magdy H. Selim, Yingting Zheng, Ruinan Shen, Lipeng Sun et al.. Alzheimer s & Dementia, 2025-05-01
Topic: Brain proteins, microglia and lab models
At baseline, Aβ+ participants showed higher CP FWf, increased white matter hyperintensity (WMH) volume, and decreased diffusion tensor image analysis along the perivascular space (DTI-ALPS). In Aβ+ participants, DTI-ALPS mediated the association between CP FWf and periventricular WMH. CP FWf was associated with cortical tau accumulation, synaptic loss, hippocampal and cortical atrophy, and cognitive performance. During follow-up, CP FWf increased faster in Aβ+ participants than controls. Elevated CP FWf indicated impaired glymphatic function and AD neurodegeneration, and can be a sensitive biomarker for AD progression. The study was registered on ClinicalTrials.gov (NCT05623124). HIGHLIGHTS: This cohort study found higher free-water fraction (FWf) of the choroid plexus (CP) in amyloid beta (Aβ)+ participants. CP FWf was related to glymphatic function, brain atrophy, tau burden, synaptic loss, and cognition. Aβ+ participants showed faster growth of CP FWf than Aβ- controls during follow-up. The growth rate of CP FWf exceeded that of white matter lesion and tau accumulation in Aβ+ participants. CP FWf can serve as a sensitive imaging marker of glymphatic function and Alzheimer's disease progression.
Key findings
- At baseline, Aβ+ participants showed higher CP FWf, increased white matter hyperintensity (WMH) volume, and decreased diffusion tensor image analysis along the perivascular space (DTI-ALPS).
- In Aβ+ participants, DTI-ALPS mediated the association between CP FWf and periventricular WMH.
- CP FWf was associated with cortical tau accumulation, synaptic loss, hippocampal and cortical atrophy, and cognitive performance.
- During follow-up, CP FWf increased faster in Aβ+ participants than controls.
- Elevated CP FWf indicated impaired glymphatic function and AD neurodegeneration, and can be a sensitive biomarker for AD progression.
Why it matters
In people with amyloid-beta, a higher free-water fraction in the choroid plexus was linked to worse glymphatic function, more tau, synaptic loss, brain atrophy, and worse cognition, and it increased faster over time than in controls. This identifies a possible imaging marker of disease progression but does not test any treatment.
Study details
- Study designcohort study
- Participants216
- Evidence strengthModerate
How this study scored 61/100
Published in a peer-reviewed journal, and it is a cohort study following people over time. Scored zero for effect reported and randomised / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 59 of the 96 points we could judge it on, which is 61 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer s & Dementia) |
| Journal's citation record | 2 / 4 | Alzheimer s & Dementia: journal h-index 228 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A cohort study following people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 216 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 | 3 / 7 | Cited 31 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 10.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 4 / 6 | Cited 19.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 2 / 4 | Cited 31 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 7 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40394891) |
| Free to read | 2 / 2 | Free to read |
| Points | 59 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 59 of the 96 points we could judge it on is 61 out of 100. |
| Total | 61 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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
Xu, X., Yang, X., Zhang, J., Wang, Y., Selim, M. H., Zheng, Y., et al. (2025). Choroid plexus free‐water correlates with glymphatic function in Alzheimer's disease. Alzheimer s & Dementia. https://doi.org/10.1002/alz.70239
Vancouver
Xu X, Yang X, Zhang J, Wang Y, Selim MH, Zheng Y, et al. Choroid plexus free‐water correlates with glymphatic function in Alzheimer's disease. Alzheimer s & Dementia. 2025. doi:10.1002/alz.70239. PMID: 40394891.
BibTeX
@article{xu2025-40394891,
author = {Xu, Xiaomeng and Yang, Xinyuan and Zhang, Junfang and Wang, Yan and Selim, Magdy H. and Zheng, Yingting and Shen, Ruinan and Sun, Lipeng and others},
title = {{Choroid plexus free‐water correlates with glymphatic function in Alzheimer's disease}},
journal = {Alzheimer s \& Dementia},
year = {2025},
doi = {10.1002/alz.70239},
pmid = {40394891},
url = {https://doi.org/10.1002/alz.70239}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.