Tomas Kavanagh, Kaleah Balcomb, Stephanie Trgovcevic, Laura Nementzik, Evgeny Kanshin, Glenda Halliday, Beatrix Ueberheide, Eleanor Drummond
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We assessed differences in the soluble fraction, insoluble fraction, and protein solubility changes between diseases, followed by enrichment and correlation analysis.</p>\n </section>\n \n <section>\n \n <h3> RESULTS</h3>\n \n <p>CBD 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.</p>\n </section>\n \n <section>\n \n <h3> DISCUSSION</h3>\n \n <p>We have contrasted the solubility patterns of proteins across three tauopathies for the first time. Protein solubility differences reveal divergence in disease processes.</p>\n </section>\n \n <section>\n \n <h3> Highlights</h3>\n \n <div>\n <ul>\n \n <li>Tau isoforms are differentially soluble in primary tauopathies</li>\n \n <li>PSP proteomics profile was the most divergent of the tauopathies examined</li>\n \n <li>SORT1 is highly insoluble in CBD and aggregates to different extents in tauopathies</li>\n \n <li>There are shifts in solubility for key signalling pathways; ROCK1 and JAK2</li>\n \n <li>Unique lysosomal proteins are more insoluble in distinct tauopathies</li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0000,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70401","citationCount":"0","resultStr":"{\"title\":\"Differences in the soluble and insoluble proteome between primary tauopathies\",\"authors\":\"Tomas Kavanagh, Kaleah Balcomb, Stephanie Trgovcevic, Laura Nementzik, Evgeny Kanshin, Glenda Halliday, Beatrix Ueberheide, Eleanor Drummond\",\"doi\":\"10.1002/alz.70401\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> INTRODUCTION</h3>\\n \\n <p>Primary 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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> METHODS</h3>\\n \\n <p>We performed sarkosyl fractionation of <i>post mortem</i> human brain tissue to enrich soluble and insoluble proteins from CBD, PiD, and PSP cases (<i>n</i> = 5/group). We assessed differences in the soluble fraction, insoluble fraction, and protein solubility changes between diseases, followed by enrichment and correlation analysis.</p>\\n </section>\\n \\n <section>\\n \\n <h3> RESULTS</h3>\\n \\n <p>CBD 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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> DISCUSSION</h3>\\n \\n <p>We have contrasted the solubility patterns of proteins across three tauopathies for the first time. 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Differences in the soluble and insoluble proteome between primary tauopathies
INTRODUCTION
Primary 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.
METHODS
We 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.
RESULTS
CBD 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
期刊介绍：
Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.
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