Evidence map›Paper›PMID 42811341›Full record

ArticleMolecular neurodegeneration2026

The YTHDF proteins modulate Alzheimer's disease-associated brain gene signatures.

Shinya Tasaki, Denis R Avey, Nicola A Kearns, Chunjiang Yu, Sashini De Tissera, Himanshu Vyas, Lin Cheng, Jishu Xu, Artemis Iatrou, Daniel J Flood and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular neurodegeneration, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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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.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors.

Shinya TasakiRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, 60612, USA. stasaki@gmail.com.
Denis R AveyRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, 60612, USA.
Nicola A KearnsRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, 60612, USA.
Chunjiang YuRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, 60612, USA.
Sashini De TisseraRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, 60612, USA.
Himanshu VyasRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, 60612, USA.
Lin ChengRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, 60612, USA.
Jishu XuRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, 60612, USA.
Artemis IatrouRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, 60612, USA.
Daniel J FloodRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, 60612, USA.
Wenlong LiDepartment of Chemistry, Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, Howard Hughes Medical Institute, University of Chicago, Chicago, IL, USA.
Lisa L BarnesRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, 60612, USA.
Katherine RothamelCenter for RNA Technologies and Therapeutics, Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, 92093, USA.
Aliza P WingoDepartment of Psychiatry, University of California, Davis, CA, 95817, USA.
Thomas S WingoDepartment of Neurology, University of California, Davis, CA, 95817, USA.
Nicholas T SeyfriedDepartment of Biochemistry, Emory University School of Medicine, Atlanta, GA, 30322, USA.
Chuan HeDepartment of Chemistry, Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, Howard Hughes Medical Institute, University of Chicago, Chicago, IL, USA.
Philip L De JagerDepartment of Neurology and the Taub Institute for the Study of Alzheimer's Disease and the Aging Brain, Center for Translational and Computational Neuroimmunology, Columbia University Medical Center, New York, NY, 10032, USA.
Gene W YeoCenter for RNA Technologies and Therapeutics, Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, 92093, USA.
Chris GaiteriRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, 60612, USA.
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, 60612, USA.
Yanling WangRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, 60612, USA. yanling_wang@rush.edu.

Funding

Alzheimer's Disease Genetics ConsortiumU01AG032984 · NIA · UNIVERSITY OF PENNSYLVANIA · PI SCHELLENBERG, GERARD DAVID · 2009 to 2024
$60.4M
SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI LEURGANS, SUE E. · 1991 to 2020
$49.1M
EPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3M
Rush Alzheimer's Disease Research CenterP30AG072975 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI Lisa L Barnes, Julie A. Schneider · 2021 to 2026
$24.7M
RISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4M
Risk Factors for Cognitive Decline in African-AmericansR01AG022018 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BARNES, LISA L · 2004 to 2025
$18.2M
Multi-omic network-directed proteoform discovery, dissection and functional validation to prioritize novel AD therapeutic targetsU01AG061356 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2018 to 2022
$13.7M
Pathway discovery, validation and compound identification for Alzheimer's disease - SupplementU01AG046152 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2013 to 2017
$13.6M
Supplement to AMP-AD Brain Proteomic Network Enhancement, Validation and Translation into CSF BiomarkersU01AG061357 · NIA · EMORY UNIVERSITY · PI LEVEY, ALLAN I, SEYFRIED, NICHOLAS THOMAS · 2018 to 2022
$9.1M
Characterizing the Behavior Profile of Healthy Cognitive AgingR01AG034374 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI PATRICIA A BOYLE · 2009 to 2026
$8.8M
Discovery of Novel Proteomic Targets in Alzheimer's DiseaseU01AG046161 · NIA · EMORY UNIVERSITY · PI BENNETT, DAVID ALAN, GESCHWIND, DANIEL H · 2014 to 2018
$8.4M
Genetic Epidemiology of Cognitive Decline in an Aging Population SampleR01AG030146 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI EVANS, DENIS A · 2007 to 2018
$6.2M
NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG072975NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG022018NIA NIH HHS R01 AG030146NIA NIH HHS R01 AG034374NIA NIH HHS R01 AG036836NIA NIH HHS R01 AG042210NIA NIH HHS R01 AG057911NIA NIH HHS R01 AG061798NIA NIH HHS R01 AG072120NIA NIH HHS R01 AG074082NIA NIH HHS R01 AG079223NIA NIH HHS R01 AG095602NIA NIH HHS RF1 AG015819NIA NIH HHS RF1 AG036042NIA NIH HHS RF1 AG074549NIA NIH HHS U01 AG032984NIA NIH HHS U01 AG046152NIA NIH HHS U01 AG046161NIA NIH HHS U01 AG061356NIA NIH HHS U01 AG061357NIA NIH HHS U01 AG079847
6 · The paper itself

Abstract

Gene signatures of Alzheimer's disease (AD) brains reflect the output of a complex interplay of genetic, epigenetic, epi-transcriptomic, and post-transcriptional regulations. To nominate candidate factors modulating these signatures, we developed a machine learning model to integrate cellular and molecular features explaining differential gene expression in AD. Among the features tested, YTHDF proteins, the canonical readers of N6-methyladenosine (m6A) RNA modification, are among the most influential predictors of AD gene signatures. Protein modules containing YTHDFs were downregulated in human AD brains, and knockdown or pharmacological inhibition of YTHDFs in iPSC-derived 2D and 3D neuronal models recapitulated key AD-associated gene signatures. Furthermore, eCLIP-seq revealed altered YTHDF binding to transcripts in AD brains, at both m6A-dependent and m6A-independent sites. Together, these results support an important role for YTHDF proteins in modulating AD-associated gene signatures in the human brain.

Indexed as

Alzheimer DiseaseBrainNerve Tissue ProteinsRNA-Binding ProteinsHumansTranscriptomeNerve Tissue ProteinsRNA-Binding ProteinsAlzheimer's diseaseCognitive declineCortical organoidsCRISPR knockouteCLIP-seqEpitranscriptomicsGene expression signaturesMachine learningPost-transcriptional regulationSmall-molecule YTHDF inhibition

Identifiers

PMID42811341
PMCPMC13625320

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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.