PXD062722-1

PXD062722 is an original dataset announced via ProteomeXchange.

Title	Proteomics of the temporal cortex in Semantic Dementia reveals brain-region specific molecular pathology and regulation of the TDP-43-ANXA11 interactome
Description	Semantic dementia (SD) is a clinical subtype of frontotemporal dementia characterized by impaired word comprehension and semantic memory, and occurs nearly always sporadically. Neuroimaging typically reveals asymmetric, predominantly left-sided, atrophy of the anterior temporal pole, anterior fusiform gyrus, and the hippocampus. Post-mortem pathological examination shows frontotemporal lobar degeneration TDP type C, characterized by long dystrophic neurites in the temporal cortex and typical round, TDP-43-positive neuronal inclusions in the dentate gyrus. While neuronal loss in the temporal cortex is severe in the end stage of disease, the dentate gyrus seems relatively spared. This characteristic and well-defined disease profile suggests SD patients share a specific underlying disease biology. Recently, we performed the first quantitative proteomic study of the dentate gyrus, uncovering potential SD-specific biological pathways. Here, we report on the first quantitative proteomic study of the temporal cortex in SD. We studied the same patient and non-demented control cohort, enabling comparative analysis between the two brain regions. In addition, we compared our dataset with other frontotemporal lobar degeneration subtypes and Alzheimer’s disease to separate SD disease-specific changes from common neurodegenerative processes. In the temporal cortex, involvement of the ribonucleoprotein complex and presynaptic regulation of cytosolic calcium levels by voltage-gated calcium channels appear unique facets of the SD disease process. Furthermore, we observed a striking difference in the abundance of neuropathological proteins TDP-43 and ANXA11, and their interactors between the temporal cortex and dentate gyrus. The elucidation of these potentially unique disease-specific mechanisms improves our understanding of the pathophysiological processes in SD and paves the way for the discovery of novel therapeutic targets.
HostingRepository	PRIDE
AnnounceDate	2026-01-16
AnnouncementXML	Submission_2026-01-16_04:50:41.778.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: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro 2

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-08 03:10:47	ID requested
⏵ 1	2026-01-16 04:50:43	announced

Miedema SSM, Rajicic A, Mol MO, Paliukhovich I, Klaassen RV, van Buuren R, Li KW, Koopmans FTW, Seelaar H, van Rooij JGJ, Smit AB, van Swieten JC, Proteomics of the temporal cortex in semantic dementia reveals brain-region specific molecular pathology and regulation of the TDP-43-ANXA11 interactome. Acta Neuropathol Commun, 13(1):162(2025) [pubmed]

10.1186/s40478-025-02077-x;

10.1186/s40478-022-01499-1;

Mol MO, Miedema SSM, Melhem S, Li KW, Koopmans F, Seelaar H, Gottmann K, Lessmann V, Bank NB, Smit AB, van Swieten JC, van Rooij JGJ, Proteomics of the dentate gyrus reveals semantic dementia specific molecular pathology. Acta Neuropathol Commun, 10(1):190(2022) [pubmed]

submitter keyword: Semantic dementia

FTLD-TDP type C

temporal cortex

quantitative proteomics

RNP complex

presynaptic regulation calcium levels

TARDBP-ANXA11 interactome

immunohistochemistry

A.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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/01/PXD062722

PRIDE project URI

• PRIDE
  1. PXD062722
     1. Label: PRIDE project
     2. Name: Proteomics of the temporal cortex in Semantic Dementia reveals brain-region specific molecular pathology and regulation of the TDP-43-ANXA11 interactome