Evidence map›Paper›PMID 37790438›Full record

ArticlebioRxiv : the preprint server for biology2023

Cryo-EM structure of Alzheimer's disease tau filaments with PET ligand MK-6240.

Peter Kunach, Jaime Vaquer-Alicea, Matthew S Smith, Robert Hopewell, Jim Monistrol, Luc Moquin, Joseph Therriault, Cecile Tissot, Nesrine Rahmouni, Gassan Massarweh and 6 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed, 24 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 3 institutions in 2 countries.

Peter KunachDepartment of Neurology, McGill University, Montreal, Quebec, Canada.
Jaime Vaquer-AliceaCenter for Alzheimer's and Neurodegenerative Diseases, Peter O'Donnell Jr. Brain Institute, Dallas, TX, United States.
Matthew S SmithDepartment of Pharmaceutical Chemistry, UCSF, San Francisco, CA, United States.
Robert HopewellMontreal Neurological Institute, Montreal, Quebec, Canada.
Jim MonistrolCenter for Alzheimer's and Neurodegenerative Diseases, Peter O'Donnell Jr. Brain Institute, Dallas, TX, United States.
Luc MoquinMontreal Neurological Institute, Montreal, Quebec, Canada.
Joseph TherriaultDepartment of Neurology, McGill University, Montreal, Quebec, Canada.
Cecile TissotDepartment of Neurology, McGill University, Montreal, Quebec, Canada.
Nesrine RahmouniDepartment of Neurology, McGill University, Montreal, Quebec, Canada.
Gassan MassarwehMontreal Neurological Institute, Montreal, Quebec, Canada.
Jean-Paul SoucyMontreal Neurological Institute, Montreal, Quebec, Canada.
Marie-Christine GuiotDepartment of Neurology, McGill University, Montreal, Quebec, Canada.
Brian K ShoichetDepartment of Pharmaceutical Chemistry, UCSF, San Francisco, CA, United States.
Pedro Rosa-NetoDepartment of Neurology, McGill University, Montreal, Quebec, Canada.
Marc I DiamondCenter for Alzheimer's and Neurodegenerative Diseases, Peter O'Donnell Jr. Brain Institute, Dallas, TX, United States.
Sarah H ShahmoradianCenter for Alzheimer's and Neurodegenerative Diseases, Peter O'Donnell Jr. Brain Institute, Dallas, TX, United States.
McGill University · CAMontreal Neurological Institute and Hospital · CAUniversity of California, San Francisco · US

Funding

Development and Testing of New Computational Methods for Ligand Discovery and MechanismR35GM122481 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Brian K Shoichet · 2017 to 2026
$8.5M
Molecular Biophysics Training GrantT32GM149436 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Aashish Manglik · 2023 to 2026
$1.6M
NIGMS NIH HHS R35 GM122481NIGMS NIH HHS T32 GM149436
6 · The paper itself

Abstract

Positron Emission Tomography (PET) ligands have advanced Alzheimer's disease (AD) diagnosis and treatment. Using autoradiography and cryo-EM, we identified AD brain tissue with elevated tau burden, purified filaments, and determined the structure of second-generation high avidity PET ligand MK-6240 at 2.31 Å resolution, which bound at a 1:1 ratio within the cleft of tau paired-helical filament (PHF), engaging with glutamine 351, lysine K353, and isoleucine 360. This information elucidates the basis of MK-6240 PET in quantifying PHF deposits in AD and may facilitate the structure-based design of superior ligands against tau amyloids.

Indexed as

[18F]MK-6240 PET tracerAlzheimer’s disease (AD)atomic resolutionautoradiographybinding affinitybinding agentsCryo-electron microscopy (cryo-EM)in vivo PET imagingNeurofibrillary tangles (NFTs)pi-pi aromatic stackingPositron emission tomography (PET)Tau

Identifiers

PMID37790438
PMCPMC10542181
OpenAlexW4386946861

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.