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Tau-PET subtype modifies the association between plasma p-tau217 and memory in Alzheimer’s disease
Zheng L, Ghanbarian E, Albarrán Morillo C, Younes K, Glover CM, Rabin LA, Grill JD, Ewers M et al.. medRxiv, 2026-09-28
Topic: Plasma and spinal-fluid biomarkers
INTRODUCTION Plasma p-tau217 is associated with Alzheimer’s disease pathology and memory performance, but its implications for memory may depend on fibrillar tau topography. We examined whether tau-PET subtype modified the association between plasma p-tau217 and memory. METHODS We analyzed 396 amyloid-positive, tau-positive participants spanning cognitively unimpaired, mild cognitive impairment, and dementia stages from six cohorts with tau-PET and plasma p-tau217; 301 had harmonized memory data. Tau-PET subtypes were derived using data-driven disease progression modelling. Primary cross-sectional models tested subtype×p-tau217 interactions for memory, adjusting for age, sex, education, APOE ε 4 status, and cohort. Secondary and exploratory analyses examined latent global cognition, non-memory measures, and longitudinal cognitive change. RESULTS Three tau-PET subtypes were retained: limbic-predominant, medial temporal lobe (MTL)-sparing, and posterior-predominant. Cross-sectionally, MTL-sparing participants had lower plasma p-tau217 than the other subtypes. The association between higher plasma p-tau217 and worse memory differed by subtype (interaction p =0.002) and was stronger in MTL-sparing ( B =-0.191, p <0.001) than in limbic-predominant ( B =-0.07, p =0.002) and posterior-predominant participants ( B =-0.07, p <0.001). The interaction remained significant after additional adjustment for diagnostic group ( p =0.015). This pattern also persisted after additional adjustment for PET tau burden, amyloid Centiloids, or plasma Aβ42/40; none of these biomarkers showed comparable subtype modification. Subtype modification was also observed for a global cognitive composite (interaction p =0.004) and subsequent memory decline in an exploratory analysis conditioned on baseline memory (interaction p =0.016). DISCUSSION Tau-PET subtype modified the p-tau217–memory association, suggesting that the cognitive implications of plasma p-tau217 may vary with tau topography.
Key findings
- INTRODUCTION Plasma p-tau217 is associated with Alzheimer’s disease pathology and memory performance, but its implications for memory may depend on fibrillar tau topography.
- RESULTS Three tau-PET subtypes were retained: limbic-predominant, medial temporal lobe (MTL)-sparing, and posterior-predominant.
- The interaction remained significant after additional adjustment for diagnostic group ( p =0.015).
- DISCUSSION Tau-PET subtype modified the p-tau217–memory association, suggesting that the cognitive implications of plasma p-tau217 may vary with tau topography.
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Study details
- Study designcross-sectional
- Participants396
- Evidence strengthModerate
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 39 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for 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 24 of the 62 points we could judge it on, which is 39 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (medRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| 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 | 396 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 | 24 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 24 of the 62 points we could judge it on is 39 out of 100. |
| Total | 39 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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APA 7th
Zheng, L., Ghanbarian, E., Albarrán Morillo, C., Younes, K., Glover, C. M., Rabin, L. A., et al. (2026). Tau-PET subtype modifies the association between plasma p-tau217 and memory in Alzheimer’s disease. medRxiv. https://doi.org/10.64898/2026.09.25.26363629
Vancouver
Zheng L, Ghanbarian E, Albarrán Morillo C, Younes K, Glover CM, Rabin LA, et al. Tau-PET subtype modifies the association between plasma p-tau217 and memory in Alzheimer’s disease. medRxiv. 2026. doi:10.64898/2026.09.25.26363629.
BibTeX
@article{zheng2026-ada7a142,
author = {Zheng, L. and Ghanbarian, E. and Albarrán Morillo, C. and Younes, K. and Glover, C. M. and Rabin, L. A. and Grill, J. D. and Ewers, M. and others},
title = {{Tau-PET subtype modifies the association between plasma p-tau217 and memory in Alzheimer’s disease}},
journal = {medRxiv},
year = {2026},
doi = {10.64898/2026.09.25.26363629},
url = {https://doi.org/10.64898/2026.09.25.26363629}
}