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MRI-derived periventricular diffusivity contextualizes plasma pTau217 associations with Alzheimer pathology: a discovery–validation study
Bao R, Zhang S, Wang F, Cheng W, Zhang T, Ding W.. Research Square, 2026-09-10
Topic: Plasma and spinal-fluid biomarkers
Background Plasma phosphorylated tau 217 (pTau217) is a promising scalable marker of Alzheimer pathology, but discordance with positron emission tomography (PET) limits context-free interpretation. We tested whether magnetic resonance imaging (MRI)-derived periventricular diffusivity (PVeD) modifies associations between pTau217 and Alzheimer pathology. Methods In this observational discovery–validation study, standardized pTau217 × PVeD interactions were tested for amyloid PET, tau PET, structural and vascular MRI, and cognitive outcomes in 602 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and 2,313 participants from the Health and Aging Brain Study–Health Disparities (HABS-HD). Analyses were adjusted for prespecified covariates and false discovery rate correction. Results In ADNI, pTau217 associations with amyloid Centiloid (interaction β = −0.096, 95% confidence interval [CI] − 0.154 to − 0.037; adjusted P = .018) and meta-temporal tau PET (β = −0.092, 95% CI − 0.158 to − 0.027; adjusted P = .018) were stronger at lower PVeD. Among participants with high pTau217, low PVeD was associated with faster cognitive decline than high PVeD (difference = − 0.100 Preclinical Alzheimer Cognitive Composite [PACC] units/year, 95% CI − 0.161 to − 0.038; adjusted P = .002). HABS-HD replicated the amyloid interaction (β = −0.109, 95% CI − 0.147 to − 0.070; adjusted P < .001) and multiple tau PET interactions; the high-pTau217/low-PVeD profile also declined faster (difference = − 0.037 PACC units/year; adjusted P = .002). Conclusions PVeD reproducibly contextualized associations between plasma pTau217 and PET-defined Alzheimer pathology across cohorts with different participant composition, pTau217 assays, PET tracers, and cognitive measures. The findings motivate prospective evaluation of MRI-informed interpretation of blood biomarkers, but PVeD is an indirect diffusion marker and the observational design does not establish mechanism, clinical utility, or decision thresholds.
Key findings
- Results In ADNI, pTau217 associations with amyloid Centiloid (interaction β = −0.096, 95% confidence interval [CI] − 0.154 to − 0.037; adjusted P = .018) and meta-temporal tau PET (β = −0.092, 95% CI − 0.158 to − 0.027; adjusted P = .018) were stronger at lower PVeD.
- Among participants with high pTau217, low PVeD was associated with faster cognitive decline than high PVeD (difference = − 0.100 Preclinical Alzheimer Cognitive Composite [PACC] units/year, 95% CI − 0.161 to − 0.038; adjusted P = .002).
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Study details
- Participants602
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 29 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 18 of the 62 points we could judge it on, which is 29 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 | 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 | 2 / 4 | 602 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 | 18 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 18 of the 62 points we could judge it on is 29 out of 100. |
| Total | 29 / 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
Bao, R., Zhang, S., Wang, F., Cheng, W., Zhang, T., & Ding, W. (2026). MRI-derived periventricular diffusivity contextualizes plasma pTau217 associations with Alzheimer pathology: a discovery–validation study. Research Square. https://doi.org/10.21203/rs.3.rs-10895317/v1
Vancouver
Bao R, Zhang S, Wang F, Cheng W, Zhang T, Ding W. MRI-derived periventricular diffusivity contextualizes plasma pTau217 associations with Alzheimer pathology: a discovery–validation study. Research Square. 2026. doi:10.21203/rs.3.rs-10895317/v1.
BibTeX
@article{bao2026-1e5483ae,
author = {Bao, R. and Zhang, S. and Wang, F. and Cheng, W. and Zhang, T. and Ding, W.},
title = {{MRI-derived periventricular diffusivity contextualizes plasma pTau217 associations with Alzheimer pathology: a discovery–validation study}},
journal = {Research Square},
year = {2026},
doi = {10.21203/rs.3.rs-10895317/v1},
url = {https://doi.org/10.21203/rs.3.rs-10895317/v1}
}
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