PXD061100-1

PXD061100 is an original dataset announced via ProteomeXchange.

Title	Comprehensive Profiling of Aβ40 and Aβ42 Fibril-Interacting Proteins Reveals PRKCG as a Drug-Targetable Regulator of Amyloidogenesis in Alzheimer’s Disease
Description	Proteins associated with amyloid-β (Aβ) pathology are critical biomarkers and potential therapeutic targets for Alzheimer’s disease (AD). Previous studies analyzing Aβ plaque composition relied on micro-dissected plaques from tissue samples. Here, we aimed to study the proteome associated with Aβ40- and Aβ42-plaques to identify protein constituents of Aβ plaques—actual Aβ40- and Aβ42-fibril interactors—, which might drive Aβ plaque development. Biotinylated-Aβ40, or -Aβ42, were incubated to form fibrils, with scrambled peptides used as control, and subjected to pull-down assays using protein extracts from AD and control prefrontal cortex tissues. Aβ-interacting proteins were identified by proteomics. Their dysregulation was assessed in AD tissue samples and a cellular AD model by WB, immunocytochemistry, in silico, and immunohistochemistry. We identified 185 and 874 proteins associated with Aβ40- and Aβ42-fibrils, respectively, with 78 in common. Sixteen were validated as interactors by WB and ex vivo as components of Aβ plaques by IF, displaying altered expression in AD and supporting a functional role for PRKCG in amyloidogenesis, as its modulation alters Aβ fibril formation. This study expands the Aβ plaque-associated proteome characterization, identifies novel fibril interactors, and highlight potential therapeutic targets, as the modulation of PRKCG prevent or reduce Aβ plaque formation in AD.
HostingRepository	PRIDE
AnnounceDate	2026-01-25
AnnouncementXML	Submission_2026-01-24_16:26:25.563.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ana Montero Calle
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-23 15:31:56	ID requested
⏵ 1	2026-01-24 16:26:26	announced

10.1002/ALZ.71090;

submitter keyword: None

Rodrigo Barderas
contact affiliation	Chronic Disease Programme (UFIEC), Instituto de Salud Carlos III, Majadahonda, E-28220 Madrid, Spain.
contact email	r.barderasm@isciii.es
lab head
Ana Montero Calle
contact affiliation	Instituto de Salud Carlos III
contact email	ana.monteroc@isciii.es
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/PXD061100

PRIDE project URI

• PRIDE
  1. PXD061100
     1. Label: PRIDE project
     2. Name: Comprehensive Profiling of Aβ40 and Aβ42 Fibril-Interacting Proteins Reveals PRKCG as a Drug-Targetable Regulator of Amyloidogenesis in Alzheimer’s Disease