Evidence map›Paper›PMID 42779765›Full record

ArticlebioRxiv : the preprint server for biology2026

TDP-43 dysfunction induces cryptic circular RNAs in ALS/FTD.

Dario Dattilo, Flaminia Pellegrini, Simone Barattucci, Anna-Leigh Brown, Jose Norberto S Vargas, Ariana Gatt, Ryan Morrie, Georgiana Miller, Iris Bachmutsky, Zachary McEachin and 22 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. 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.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

32 authors.

Dario DattiloUCL Queen Square Motor Neuron Disease Centre, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, UCL, London, UK.
Flaminia PellegriniUCL Queen Square Motor Neuron Disease Centre, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, UCL, London, UK.
Simone BarattucciUCL Queen Square Motor Neuron Disease Centre, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, UCL, London, UK.
Anna-Leigh BrownUCL Queen Square Motor Neuron Disease Centre, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, UCL, London, UK.
Jose Norberto S VargasUCL Queen Square Motor Neuron Disease Centre, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, UCL, London, UK.
Ariana GattDepartment of Neurodegenerative Disease, Institute of Neurology, University College London, London, UK.
Ryan MorrieTrace Neuroscience, South San Francisco, CA 94080, USA.
Georgiana MillerTrace Neuroscience, South San Francisco, CA 94080, USA.
Iris BachmutskyTrace Neuroscience, South San Francisco, CA 94080, USA.
Zachary McEachinCenter for Neurodegenerative Disease, Emory University, Atlanta, GA, 30329, USA.
Mingee ChungCenter for Neurodegenerative Disease, Emory University, Atlanta, GA, 30329, USA.
Matthew J KeussUCL Queen Square Motor Neuron Disease Centre, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, UCL, London, UK.
Eugeni RyadnovUCL Queen Square Motor Neuron Disease Centre, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, UCL, London, UK.
Matteo ZanovelloUCL Queen Square Motor Neuron Disease Centre, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, UCL, London, UK.
Puja R MehtaUCL Queen Square Motor Neuron Disease Centre, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, UCL, London, UK.
Francesca MattediUCL Queen Square Motor Neuron Disease Centre, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, UCL, London, UK.
Michela BarioglioUCL Queen Square Motor Neuron Disease Centre, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, UCL, London, UK.
Shubha KamathUCL Queen Square Motor Neuron Disease Centre, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, UCL, London, UK.
Sarah E Kargbo-HillDepartment of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI, USA.
Joanna PaladeNational Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA.
Isabelle KowalNational Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA.
Jonathan GlassDepartments of Neurology and Pathology, Emory University, Atlanta, GA, USA.
Marla GearingDepartment of Pathology and Laboratory Medicine, Department of Neurology, Goizueta Alzheimer's Disease Research Center, Emory University, Atlanta, GA, USA.
Edward B LeeDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia.
Melissa E MurrayDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Dennis W DicksonDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
NYGC ALS Consortium
Eric M GreenTrace Neuroscience, South San Francisco, CA 94080, USA.
Nicholas T SeyfriedCenter for Neurodegenerative Disease, Emory University, Atlanta, GA, 30329, USA.
Sanjay ChandrianiTrace Neuroscience, South San Francisco, CA 94080, USA.
Michael WardNational Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA.
Pietro FrattaUCL Queen Square Motor Neuron Disease Centre, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, UCL, London, UK.

Funding

Human Biomarkers CoreU54NS123743 · NINDS · STANFORD UNIVERSITY · PI FRATTA, PIETRO, GITLER, AARON D. · 2021 to 2025
$8.2M
NINDS NIH HHS U54 NS123743
6 · The paper itself

Abstract

Nuclear depletion of TDP-43 is a defining pathological feature of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), leading to widespread RNA misprocessing, including the formation of cryptic exons. Here, we identified TDP-43 as a regulator of circular RNA (circRNA) biogenesis in multiple human neuronal cell models, and showed that its dysfunction induces the de novo formation of cryptic circular RNAs (c-circRNAs). Analysis of post-mortem brain transcriptomic data identified a subset of c-circRNAs which are specific for ALS and FTD cases with TDP-43 pathology. Further, we developed highly sensitive rolling-circle amplification-based circRNA detection assays that allow to distinguish TDP-43 pathology in human CNS tissues with a 0.99 AUC. We found that c-circRNAs can co-occur with cryptic linear splicing events, uncovering complex RNA misprocessing hotspots that induce loss of disease-relevant proteins, including

Identifiers

PMID42779765
PMCPMC13596441

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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.