Evidence map›Paper›PMID 40520109›Full record

ArticleiScience2025

ALS-associated TDP-43 aggregates drive innate and adaptive immune cell activation.

Baggio A Evangelista, Joey V Ragusa, Kyle Pellegrino, Yijia Wu, Ivana Yoseli Quiroga-Barber, Shannon R Cahalan, Omeed K Arooji, Jillann A Madren, Sally Schroeter, Joe Cozzarin and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in iScience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Article
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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

19 authors.

Baggio A EvangelistaDepartment of Neurology, University of North Carolina, Chapel Hill, NC, USA.
Joey V RagusaDepartment of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC, USA.
Kyle PellegrinoDepartment of Pharmacology, University of North Carolina, Chapel Hill, NC, USA.
Yijia WuThurston Arthritis Research Center, University of North Carolina, Chapel Hill, NC, USA.
Ivana Yoseli Quiroga-BarberThurston Arthritis Research Center, University of North Carolina, Chapel Hill, NC, USA.
Shannon R CahalanMedical Student Training in Aging Research, Center for Aging and Health, University of North Carolina, Chapel Hill, NC, USA.
Omeed K AroojiDepartment of Neurology, University of North Carolina, Chapel Hill, NC, USA.
Jillann A MadrenMicroscopy Services Laboratory, Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Sally SchroeterStandard BioTools Discovery Lab, Standard BioTools Inc., Markham, ON, Canada.
Joe CozzarinStandard BioTools Discovery Lab, Standard BioTools Inc., Markham, ON, Canada.
Ling XieDepartment of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC, USA.
Xian ChenDepartment of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC, USA.
Kristen K WhiteMicroscopy Services Laboratory, Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
J Ashley EzzellDepartment of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC, USA.
Marie A IannoneLineberger Comprehensive Cancer Center, Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA.
Sarah CohenDepartment of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC, USA.
Douglas H PhanstielDepartment of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC, USA.
Rick B MeekerDepartment of Neurology, University of North Carolina, Chapel Hill, NC, USA.
Todd J CohenDepartment of Neurology, University of North Carolina, Chapel Hill, NC, USA.

Funding

Identifying Alzheimer’s Disease Causal Variants and Target Genes Using iPSC-derived MicrogliaR01AG066871 · NIA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI COHEN, TODD JONATHAN, PHANSTIEL, DOUGLAS H. · 2020 to 2024
$3.7M
NIA NIH HHS R01 AG066871
6 · The paper itself

Abstract

Amyotrophic lateral sclerosis (ALS) is the most common and fatal motor neuron disease. Approximately 90% of ALS patients exhibit pathology of the master RNA regulator, transactive response DNA binding protein (TDP-43). Despite the prevalence TDP-43 pathology in ALS motor neurons, recent findings suggest immune dysfunction is a determinant of disease progression in patients. Whether TDP-43 aggregates elicit immune responses remains underexplored. In this study, we demonstrate that TDP-43 aggregates are internalized by antigen-presenting cell populations, cause vesicle rupture, and drive innate and adaptive immune cell activation by way of antigen presentation. Using a multiplex imaging platform, we observed enrichment of activated microglia/macrophages in ALS white matter that correlated with phosphorylated TDP-43 accumulation, CD8 T cell infiltration, and major histocompatibility complex expression. Taken together, this study sheds light on a novel cellular response to TDP-43 aggregates through an immunological lens.

Indexed as

ImmunityNeuroscienceOmics

Identifiers

PMID40520109
PMCPMC12167492

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.