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Evaluation of [18F]MK-6240 binding to tau protein in postmortem human brains of Down syndrome and Alzheimer’s disease and assessment of off-target (non-tau) binding
Karim F, Biju AP, Liang C, Santos CJ, Rajarethenam M, Mukherjee J.. Research Square, 2026-01-06
Topic: Disease mechanisms in lab and animal studies
Alzheimer's disease (AD) and Down Syndrome (DS) are characterized by the aggregation of tau tangles. As a novel tau PET tracer in AD, [ 18 F]MK-6240 has the potential in DSAD to elucidate pathophysiology and advance diagnostic strategies. Autoradiography of frontal cortex (FCX) and temporal cortex (TCX) postmortem brain slices of DSAD (n = 5), AD (n = 5), and cognitively normal (CN) (n = 5) cases indicated similarly high [ 18 F]MK-6240 binding in DSAD and AD cases. Anti-tau immunostains confirmed total tau presence so there was alignment in anti-tau abundance with quantification of [ 18 F]MK-6240 binding. DSAD and AD cases exhibited higher gray matter (GM)/white matter (WM) ratios of 2.8 and 2.5 respectively. For drug effects on [ 18 F]MK-6240 binding, self-displacement of [ 18 F]MK-6240 was by 88% among DSAD cases and 85% among AD cases while IPPI displaced [ 18 F]MK-6240 by 81% and 74% in DSAD and AD cases respectively. KuFal194, a specific phosphokinase inhibitor, minimally displaced [ 18 F]MK-6240 binding. Harmine competed with [ 18 F]MK-6240 with an IC 50 value of 290 ± 218 nM and 92 ± 15 nM for DSAD and AD cases, respectively, suggesting unique tau binding. High meninges off-target (non-tau) binding of [ 18 F]MK-6240 was observed in a CN case, comparable to the GM in DSAD and AD. MK-6240 (10 µM) blocked 44% and T807 (10 µM) blocked 30% of meninges binding. Incubation of meninges in the presence of 0.2% polyethylenimine reduced 70% of [ 18 F]MK-6240 binding. The tau imaging agent, [ 125 I]IPPI, an analog of [ 18 F]MK-6240, exhibited minimal binding to CN meninges. Our findings suggest [ 18 F]MK-6240 to be selective tau imaging agent in DSAD and AD, harmine to be a weak tau drug, and off-target nonspecific meninges binding maybe due to the primary aromatic amine group in [ 18 F]MK-6240.
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APA 7th
Karim, F., Biju, A. P., Liang, C., Santos, C. J., Rajarethenam, M., & Mukherjee, J. (2026). Evaluation of [18F]MK-6240 binding to tau protein in postmortem human brains of Down syndrome and Alzheimer’s disease and assessment of off-target (non-tau) binding. Research Square. https://doi.org/10.21203/rs.3.rs-8463304/v1
Vancouver
Karim F, Biju AP, Liang C, Santos CJ, Rajarethenam M, Mukherjee J. Evaluation of [18F]MK-6240 binding to tau protein in postmortem human brains of Down syndrome and Alzheimer’s disease and assessment of off-target (non-tau) binding. Research Square. 2026. doi:10.21203/rs.3.rs-8463304/v1.
BibTeX
@article{karim2026-c556b929,
author = {Karim, F. and Biju, A. P. and Liang, C. and Santos, C. J. and Rajarethenam, M. and Mukherjee, J.},
title = {{Evaluation of [18F]MK-6240 binding to tau protein in postmortem human brains of Down syndrome and Alzheimer’s disease and assessment of off-target (non-tau) binding}},
journal = {Research Square},
year = {2026},
doi = {10.21203/rs.3.rs-8463304/v1},
url = {https://doi.org/10.21203/rs.3.rs-8463304/v1}
}
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Key findings
- Our findings suggest [ 18 F]MK-6240 to be selective tau imaging agent in DSAD and AD, harmine to be a weak tau drug, and off-target nonspecific meninges binding maybe due to the primary aromatic amine group in [ 18 F]MK-6240.
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Study details
- Effect size0.2%
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 24 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, studied in people 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 15 of the 62 points we could judge it on, which is 24 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 | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| 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 | 15 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 15 of the 62 points we could judge it on is 24 out of 100. |
| Total | 24 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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