Evidence map›Paper›PMID 40985163›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025

Quantitative Profiling of Nanoscopic Protein Aggregates Reveals Specific Fingerprint of TDP-43-Positive Assemblies in Motor Neuron Disease.

Dezerae Cox, Melanie Burke, Sara Milani, Matthew A White, Fergal M Waldron, Dorothea Böken, Evgeniia Lobanova, Jemeen Sreedharan, Jenna M Gregory, David Klenerman

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
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

10 authors.

Dezerae CoxYusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, UK.ORCID https://orcid.org/0000-0002-5345-8360
Melanie BurkeYusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, UK.
Sara MilaniMaurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 9RT, UK.ORCID https://orcid.org/0009-0002-1200-7755
Matthew A WhiteMaurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 9RT, UK.ORCID https://orcid.org/0000-0002-4147-4267
Fergal M WaldronInstitute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK.ORCID https://orcid.org/0000-0003-2622-0776
Dorothea BökenYusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, UK.ORCID https://orcid.org/0009-0008-8443-4469
Evgeniia LobanovaYusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, UK.ORCID https://orcid.org/0000-0002-7605-5820
Jemeen SreedharanMaurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 9RT, UK.ORCID https://orcid.org/0000-0002-8682-6844
Jenna M GregoryInstitute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK.ORCID https://orcid.org/0000-0003-3337-4079
David KlenermanYusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, UK.ORCID https://orcid.org/0000-0001-7116-6954

Funding

Alzheimer's Research UK Research Fellowship ARUK-RF2020A-008MND Association UK Cox 971-799MND Association UK Gregory/APR24/2374-791Parkinson's UK G-1901Rosetrees Trust CF2\100004Target ALS BB-2022-C4-L2Wellcome TrustWellcome Trust Senior Research Fellowship 221824/Z/20/Z
6 · The paper itself

Abstract

Abnormal aggregation of TAR DNA-binding protein 43 (TDP-43) is a pathological hallmark of motor neuron disease (MND), yet current methods for quantifying these aggregates in biological samples remain limited in sensitivity and resolution. Here, single-molecule fluorescence microscopy is applied to post-mortem brain extracts to quantitatively characterize aggregates containing TDP-43 at the individual particle level. The resulting aggregate fingerprints, consisting of morphological and compositional profiles, are sufficient to distinguish MND donors from neurologically normal controls and further discriminate between clinically distinct MND subgroups. Comparative proteomic analysis confirms and extends these findings, revealing convergent and complementary molecular signatures. These results demonstrate, for the first time, that single-molecule aggregate profiling can stratify MND cases using patient-derived tissues, paving the way for the development of sensitive minimally invasive diagnostics and mechanistically informed disease monitoring tools.

Indexed as

DNA-Binding ProteinsMotor Neuron DiseaseProtein AggregatesAgedBrainFemaleHumansMaleMicroscopy, FluorescenceMiddle AgedProteomicsSingle Molecule ImagingDNA-Binding ProteinsProtein AggregatesTARDBP protein, humanmotor neuron diseaseprotein aggregatesproteomicssingle‐molecule microscopy

Identifiers

PMID40985163
PMCPMC12667529

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Registered trials

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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.