Evaluation of [

Fariha Karim, Agnes P Biju, Christopher Liang, Camryn J Santos, Maharishi Rajarethenam, Jogeshwar Mukherjee

Abstract read

In one paragraph

Article in Acta neuropathologica communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it

0cells of the map it votes in

1citing papers in PubMed

–field-weighted citation impact

1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

Measurement of Tau Protein and Aβ Amyloid Plaques in Postmortem Human Brains of Down Syndrome and Alzheimer's Disease by Using [Synapse (New York, N.Y.) · 2026
Article

4 · The record

Corrections and comments

Update of
Evaluation of [2026

5 · Who and what money

Authors and funding

6 authors.

Fariha KarimPreclinical Imaging, Department of Radiological Sciences, University of California-Irvine, Medical Sciences B138, Irvine, CA, 92697-5000, USA. fkarim1@uci.edu.

Agnes P BijuPreclinical Imaging, Department of Radiological Sciences, University of California-Irvine, Medical Sciences B138, Irvine, CA, 92697-5000, USA.

Christopher LiangPreclinical Imaging, Department of Radiological Sciences, University of California-Irvine, Medical Sciences B138, Irvine, CA, 92697-5000, USA.

Camryn J SantosPreclinical Imaging, Department of Radiological Sciences, University of California-Irvine, Medical Sciences B138, Irvine, CA, 92697-5000, USA.

Maharishi RajarethenamPreclinical Imaging, Department of Radiological Sciences, University of California-Irvine, Medical Sciences B138, Irvine, CA, 92697-5000, USA.

Jogeshwar MukherjeePreclinical Imaging, Department of Radiological Sciences, University of California-Irvine, Medical Sciences B138, Irvine, CA, 92697-5000, USA. mukherjj@hs.uci.edu.

Funding

Novel Tau-Targeted Radiohalogenated Agents for Alzheimer's DiseaseR01AG077700 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI Jogeshwar Mukherjee · 2024 to 2026

$2.1M

NIA NIH HHS R01 AG077700NIH HHS R01AG077700

6 · The paper itself

Abstract

Alzheimer's disease (AD) and Down Syndrome (DS) are characterized by the aggregation of tau tangles. As a novel tau PET tracer in AD, [18F]MK-6240 has the potential in Down syndrome-associated Alzheimer’s disease (DSAD) to elucidate pathophysiology and advance diagnostic strategies. Autoradiography of frontal cortex and temporal cortex postmortem brain slices of DSAD (n = 5), AD (n = 5), and cognitively normal (CN) (n = 5) cases indicated similarly high [18F]MK-6240 binding in DSAD and AD cases. [18F]MK-6240 binding in CN was substantially less than DSAD and AD. Anti-tau immunostains confirmed total tau presence that aligned with the localization of [18F]MK-6240 binding. DSAD and AD cases exhibited higher gray matter (GM)/white matter ratios of 2.8 and 2.5 respectively. For drug effects on [18F]MK-6240 binding, self-displacement by MK-6240 (10 µM) reduced binding by 88% among DSAD cases and 85% among AD cases while IPPI (10 µM) displaced [18F]MK-6240 by 81% and 74% in DSAD and AD cases respectively. KuFal194 (10 µM), a specific phosphokinase inhibitor, minimally displaced [18F]MK-6240 binding. Harmine competed with [18F]MK-6240 with an IC50 value of 290 nM and 92 nM for DSAD and AD cases, respectively. High meninges off-target (non-tau) binding of [18F]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% polyethyleneimine reduced 70% of [18F]MK-6240 binding. The tau radioligand, [125I]IPPI, an analog of [18F]MK-6240, exhibited minimal binding to CN meninges compared to the DSAD and AD cases. Our findings suggest [18F]MK-6240 to be selective tau imaging agent in DSAD and AD, harmine to uniquely compete with [18F]MK-6240 binding in DSAD and provide preliminary insights to the off-target nonspecific binding of [18F]MK-6240 in postmortem meninges.

Indexed as

Alzheimer DiseaseBrainDown SyndromeIsoquinolinestau ProteinsAgedAged, 80 and overAutoradiographyFemaleFluorine RadioisotopesHumansMaleMiddle AgedPositron-Emission TomographyProtein BindingRadiopharmaceuticalsFluorine RadioisotopesIsoquinolinesMK-6240Radiopharmaceuticalstau ProteinsAlzheimer’s diseaseDown syndromeImagingMeningesPETTau

Identifiers

PMID41832540

DOI10.1186/s40478-026-02267-1

PMCPMC13107810

What OpenQuestion holds

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LicenceCC BY

Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.