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Detection of tau spatial extent using MK6240 and flortaucipir PET
Povala G, Bellaver B, Amaral L, Lussier FZ, Macedo AC, Ferreira PC, Leffa DT, Bauer-Negrini G et al.. medRxiv, 2026-10-28
Topic: Plasma and spinal-fluid biomarkers
INTRODUCTION Tau PET enables in vivo quantification of neurofibrillary tangle spread, yet whether tau spatial extent (TSE) performs comparably across tracers remains unknown. METHODS We performed a head-to-head comparison of Flortaucipir and MK6240 tau PET in 682 individuals across the AD continuum, quantifying TSE as the percentage of regional voxels exceeding a tracer-specific abnormality threshold and evaluated it as a metric of tracer comparability. RESULTS MK6240 showed greater TSE than Flortaucipir (CU Aβ+, medial temporal lobe [MTL]: 42% vs 25%; dementia Aβ+, late neocortical: 55% vs 42%), reaching 50% detection probability at lower Aβ burden (Centiloid: MTL, 26 vs 45; late neocortical, 95 vs 118). TSE showed higher associations than SUVR with memory, Aβ PET, and plasma pTau217, particularly in the neo-late composite. Participants with intermediate tau involvement (TSE 25–50%), most below the SUVR positivity thresholds (MTL positivity 10.2–16.9%), had approximately three-fold higher odds of Aβ PET and pTau217 positivity than TSE 0–25% (ORs 2.90–3.46). 53.4% of intermediate Flortaucipir cases (TSE 25–50%) shifted to a higher MK6240 category, and 82.5% of moderately high Flortaucipir cases (50–75%) were classified as near-saturated (75–100%) by MK6240. Neither raw TSE nor raw SUVR was directly interchangeable across tracers, with systematic and proportional bias for both metrics (MTL Deming slope: TSE 1.29; SUVR 2.69). DISCUSSION TSE showed stronger unadjusted associations than SUVR in selected region- and outcome-specific comparisons, supporting its potential as a complementary measure. Like SUVR, raw TSE values were not directly interchangeable between flortaucipir and MK6240, and tracer-specific calibration and validation are required before cross-tracer use.
Key findings
- RESULTS MK6240 showed greater TSE than Flortaucipir (CU Aβ+, medial temporal lobe [MTL]: 42% vs 25%; dementia Aβ+, late neocortical: 55% vs 42%), reaching 50% detection probability at lower Aβ burden (Centiloid: MTL, 26 vs 45; late neocortical, 95 vs 118).
- Participants with intermediate tau involvement (TSE 25–50%), most below the SUVR positivity thresholds (MTL positivity 10.2–16.9%), had approximately three-fold higher odds of Aβ PET and pTau217 positivity than TSE 0–25% (ORs 2.90–3.46). 53.4% of intermediate Flortaucipir cases (TSE 25–50%) shifted to a higher MK6240 category, and 82.5% of moderately high Flortaucipir cases (50–75%) were classified as near-saturated (75–100%) by MK6240.
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Study details
- Participants682
- Effect size16.9%; 53.4%; 82.5%
- Evidence strengthLow
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 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 (medRxiv) |
| 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 | 682 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| 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. |
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APA 7th
Povala, G., Bellaver, B., Amaral, L., Lussier, F. Z., Macedo, A. C., Ferreira, P. C., et al. (2026). Detection of tau spatial extent using MK6240 and flortaucipir PET. medRxiv. https://doi.org/10.64898/2026.10.26.26366488
Vancouver
Povala G, Bellaver B, Amaral L, Lussier FZ, Macedo AC, Ferreira PC, et al. Detection of tau spatial extent using MK6240 and flortaucipir PET. medRxiv. 2026. doi:10.64898/2026.10.26.26366488.
BibTeX
@article{povala2026-5c9de0fb,
author = {Povala, G. and Bellaver, B. and Amaral, L. and Lussier, F. Z. and Macedo, A. C. and Ferreira, P. C. and Leffa, D. T. and Bauer-Negrini, G. and others},
title = {{Detection of tau spatial extent using MK6240 and flortaucipir PET}},
journal = {medRxiv},
year = {2026},
doi = {10.64898/2026.10.26.26366488},
url = {https://doi.org/10.64898/2026.10.26.26366488}
}
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