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PXD033060

PXD033060 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleProteomics of the dentate gyrus reveals semantic dementia specific molecular pathology
DescriptionBackground Semantic dementia (SD) is a subtype of frontotemporal dementia (FTD) characterized by language deficits due to severe temporal lobe degeneration. The consistent neuropathological diagnosis is FTD-TDP subtype C, with characteristic round TDP-43 protein inclusions in the dentate gyrus. Despite this striking clinicopathological concordance, the pathogenic mechanisms are largely unexplained forestalling the development of targeted therapeutics. Methods We carried out laser capture microdissection of the dentate gyrus of 15 SD patients and 17 non-demented controls, and assessed relative protein abundance changes by label-free quantitative mass spectrometry. To identify SD specific proteins, we compared our results to eight other FTD and Alzheimer’s disease (AD) proteomic datasets of cortical brain tissue, parallel with functional enrichment analyses and protein-protein interactions (PPI). Results Of the total 5,354 quantified proteins, 151 showed differential abundance (FDR<1%) in SD patients. Seventy-two proteins were previously found altered with the same directional change in at least one FTD/AD proteomic study, while 79 proteins were considered as showing potentially SD specific dysregulation. Functional enrichment indicated an overrepresentation of pathways related to the immune response, metabolic processes, and cell-junction assembly. PPI analysis highlighted a cluster of interacting proteins associated with adherens junction and cadherin binding– the cadherin-catenin complex. Multiple proteins in this complex showed strong and apparent specific upregulation in SD, including β-catenin (CTNNB1), γ-catenin (JUP), and N-cadherin (CDH2). Conclusions We discovered an increase of cell adhesion proteins in SD specifically constituting the cadherin-catenin complex at the synaptic membrane, essential for synaptic signaling. Although further validation is warranted, we anticipate that these findings will help unravel the disease processes underlying SD.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_08:55:07.476.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterSuzanne Miedema
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue; monohydroxylated residue
InstrumentTripleTOF 5600
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-04-07 03:25:06ID requested
12023-03-10 12:37:24announced
22023-11-14 08:55:08announced2023-11-14: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Semantic dementia, proteomics, mass spectrometry, frontotemporal dementia, TDP-43
Contact List
August B. Smit
contact affiliationDepartment of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
contact emailguus.smit@vu.nl
lab head
Suzanne Miedema
contact affiliationVrije Universiteit Amsterdam
contact emails.s.m.miedema@vu.nl
dataset submitter
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Dataset FTP location
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