PXD062998

PXD062998 is an original dataset announced via ProteomeXchange.

Title	Spatial Multi-Omics Identifies Early Synaptic Pruning and Context-Specific Dopaminergic Vulnerability in Synucleinopathies
Description	Parkinson’s disease (PD) is characterized by degeneration of dopaminergic neurons in the substantia nigra pars compacta, but the molecular events preceding neuronal loss remain unclear. Here, we combine spatial transcriptomics, spatial proteomics, and α-synuclein (αSyn) seed amplification assays to profile post-mortem midbrain tissue from controls, incidental Lewy body disease (iLBD), PD, Alzheimer’s disease (AD), and AD with Lewy body pathology (AD+LBP). We find that αSyn seeding activity correlates with dopaminergic neuron loss in PD-spectrum cases but not in AD-associated LBP, indicating disease-context dependent relationships between αSyn pathology and neurodegeneration. In iLBD, before overt substantia nigra Lewy pathology or detectable αSyn aggregation, we detect increased expression of the complement component C1QC together with loss of inhibitory synaptic markers. These findings support early complement-associated remodeling of inhibitory synapses as a potential pathogenic event preceding overt αSyn aggregation and neuronal degeneration in PD.
HostingRepository	PRIDE
AnnounceDate	2026-06-10
AnnouncementXML	Submission_2026-06-09_16:07:41.373.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Karsten Nalbach
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-15 14:06:41	ID requested
⏵ 1	2026-06-09 16:07:41	announced

Dataset with its publication pending

submitter keyword: Human, Brain, PD, iLBD, SN, fibers

Stefan Lichtenthaler
contact affiliation	Deutsches Zentrum für Neurodegeneration (DZNE) Technische Universität München
contact email	stefan.lichtenthaler@dzne.de
lab head
Karsten Nalbach
contact affiliation	DZNE Munich / TU Munich
contact email	karsten.nalbach@dzne.de
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/2026/06/PXD062998

PRIDE project URI

• PRIDE
  1. PXD062998
     1. Label: PRIDE project
     2. Name: Spatial Multi-Omics Identifies Early Synaptic Pruning and Context-Specific Dopaminergic Vulnerability in Synucleinopathies