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Journal article

Extracellular vesicles in TDP-43 proteinopathies: pathogenesis and biomarker potential

Abstract:
Extracellular vesicles (EVs) are membrane-enclosed nanoparticles released by most cell types, and from multiple sub-cellular compartments. They carry a range of cargo biomolecules, including protein and RNA that reflect the type and status of their cell of origin. EVs are associated with the 43 kDa trans-active response DNA binding protein (TDP-43), aggregates of which are a key pathological feature across the spectrum of amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and other TDP-43 proteinopathies. The secretion of TDP-43 via EVs may have beneficial effects through the cellular clearance of aggregated protein, or detrimental effects via the intercellular spread of templated TDP-43 aggregation. This review examines evidence for the association of TDP-43 with EVs in post mortem tissue, in vitro models and human biofluids, and discusses evidence for EV TDP-43 involvement in pathogenesis via clearance or ‘seeding’ processes. We further discuss the potential for use of EVs in biomarker development, through analysis of TDP-43 or alternative protein and RNA cargoes.
Publication status:
Published
Peer review status:
Peer reviewed

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Files:
Publisher copy:
10.1186/s13024-025-00859-4

Authors

More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Clinical Neurosciences
Role:
Author
ORCID:
0000-0002-8034-8511
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Clinical Neurosciences
Role:
Author
ORCID:
0000-0002-1577-2105
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Clinical Neurosciences
Role:
Author
ORCID:
0000-0002-5159-5070
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Clinical Neurosciences
Sub department:
Clinical Neurosciences
Role:
Author
ORCID:
0000-0003-0776-6431


More from this funder
Funder identifier:
https://ror.org/02gq0fg61
Funding agency for:
Thompson, AG
Grant:
Thompson/Jan20/952 − 795
Programme:
Lady Edith Wolfson Clinician Scientist Fellowship
More from this funder
Funder identifier:
https://ror.org/03x94j517
Funding agency for:
Thompson, AG
Grant:
MR/T006927/1


Publisher:
BioMed Central
Journal:
Molecular Neurodegeneration More from this journal
Volume:
20
Issue:
1
Article number:
68
Publication date:
2025-06-10
Acceptance date:
2025-06-03
DOI:
EISSN:
1750-1326


Language:
English
Keywords:
Pubs id:
2128162
Local pid:
pubs:2128162
Deposit date:
2025-06-05
ARK identifier:

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