PXD033060

PXD033060 is an original dataset announced via ProteomeXchange.

Title	Proteomics of the dentate gyrus reveals semantic dementia specific molecular pathology
Description	Background 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.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:55:07.476.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Suzanne Miedema
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2022-04-07 03:25:06	ID requested
1	2023-03-10 12:37:24	announced
⏵ 2	2023-11-14 08:55:08	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: Semantic dementia, proteomics, mass spectrometry, frontotemporal dementia, TDP-43

August B. Smit
contact affiliation	Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
contact email	guus.smit@vu.nl
lab head
Suzanne Miedema
contact affiliation	Vrije Universiteit Amsterdam
contact email	s.s.m.miedema@vu.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD033060
     1. Label: PRIDE project
     2. Name: Proteomics of the dentate gyrus reveals semantic dementia specific molecular pathology