Evidence map›Paper›PMID 40545554›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025

Differences in the soluble and insoluble proteome between primary tauopathies.

Tomas Kavanagh, Kaleah Balcomb, Stephanie Trgovcevic, Laura Nementzik, Evgeny Kanshin, Glenda Halliday, Beatrix Ueberheide, Eleanor Drummond

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Differences in the soluble and insoluble proteome between primary tauopathies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    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

8 authors.

Tomas KavanaghBrain and Mind Centre and School of Medical Sciences, University of Sydney, Camperdown, New South Wales, Australia.
Kaleah BalcombBrain and Mind Centre and School of Medical Sciences, University of Sydney, Camperdown, New South Wales, Australia.
Stephanie TrgovcevicBrain and Mind Centre and School of Medical Sciences, University of Sydney, Camperdown, New South Wales, Australia.
Laura NementzikBrain and Mind Centre and School of Medical Sciences, University of Sydney, Camperdown, New South Wales, Australia.
Evgeny KanshinProteomics Laboratory, Division of Advanced Research Technologies and Department of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, New York, New York, USA.
Glenda HallidayBrain and Mind Centre and School of Medical Sciences, University of Sydney, Camperdown, New South Wales, Australia.
Beatrix UeberheideProteomics Laboratory, Division of Advanced Research Technologies and Department of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, New York, New York, USA.
Eleanor DrummondBrain and Mind Centre and School of Medical Sciences, University of Sydney, Camperdown, New South Wales, Australia.ORCID 0000-0002-5466-4609

Funding

Alzheimer's Association AARG-21-852072Bluesand FoundationNHMRC Senior Leadership Fellowship 1176607TDM Foundation
6 · The paper itself

Abstract

introductionPrimary tauopathies, including corticobasal degeneration (CBD), Pick's disease (PiD), and progressive supranuclear palsy (PSP), have aggregated tau pathology in the brain. Many other proteins are likely altered in disease; however, these have not been well characterized.

methodsWe performed sarkosyl fractionation of post mortem human brain tissue to enrich soluble and insoluble proteins from CBD, PiD, and PSP cases (n = 5/group). We assessed differences in the soluble fraction, insoluble fraction, and protein solubility changes between diseases, followed by enrichment and correlation analysis.

resultsCBD and PiD showed the greatest proteomic similarity in both the soluble and insoluble fractions, while PSP was the most divergent in comparison to other diseases. We observed critical changes in the solubility of lysosomal regulators, postsynaptic proteins, the extracellular matrix (ECM), and mitochondrial proteins. DISCUSSION: We have contrasted the solubility patterns of proteins across three tauopathies for the first time. Protein solubility differences reveal divergence in disease processes. HIGHLIGHTS: Tau isoforms are differentially soluble in primary tauopathies PSP proteomics profile was the most divergent of the tauopathies examined SORT1 is highly insoluble in CBD and aggregates to different extents in tauopathies There are shifts in solubility for key signalling pathways; ROCK1 and JAK2 Unique lysosomal proteins are more insoluble in distinct tauopathies.

Indexed as

BrainCorticobasal DegenerationPick Disease of the BrainProteomeSupranuclear Palsy, ProgressiveTauopathiesAgedAged, 80 and overFemaleHumansMaleMiddle AgedProteomicsSolubilitytau ProteinsProteometau Proteinsbraincorticobasal degenerationhumaninsolublemass spectrometryPick's diseaseprogressive supranuclear palsyproteomicssarkosylsortilintautauopathy

Identifiers

PMID40545554
PMCPMC12183113

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.