PXD062640

PXD062640 is an original dataset announced via ProteomeXchange.

Title	Comprehensive and site-specific characterization of protein N-glycosylation in AD samples reveals its potential roles in protein aggregation and synaptic dysfunction
Description	Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline. Protein glycosylation plays a key role in regulating protein stability, aggregation, and synaptic function, and emerging evidence strongly suggests that glycosylation is related to this disease. However, the extent and functional consequences of site-specific N-glycosylation alterations in AD remain to be further explored. In this study, we employed a dendrimer boronic acid (DBA)-based enrichment strategy combined with multiplexes proteomics to systematically analyze protein N-glycosylation in postmortem human brain tissues. We identified 3,105 N-glycosylation sites from 1,299 glycoproteins and performed a systematic assessment of site-specific glycosylation alterations in AD. Glycoproteins involved in cholesterol efflux were upregulated, whereas those associated with chemical synaptic transmission and ion transmembrane transport were significantly downregulated in AD. We observed widespread dysregulation of N-glycosylation across multiple protein domains, particularly in the ConA-like lectins/glucanases and Zn-dependent exopeptidases domains. Notably, we identified 161 N-glycosylation sites located within aggregation-prone regions (APRs), suggesting a potential protective role of glycosylation against protein aggregation. N-glycosylation sites located within APRs on plaque-associated glycoproteins were significantly reduced in AD, highlighting their potential involvement in protein aggregation and plaque formation. Additionally, downregulated N-glycosylation sites were enriched in synaptic membrane proteins, such as Ca2+ ion channels, GABA-gated chloride channels, and glutamate receptors, implicating glycosylation loss in synaptic dysfunction. Comprehensive and site-specific characterization of N-glycosylation alterations in the AD brain tissues reveals its potential role in protein aggregation and synaptic dysfunction. Our findings suggest that the loss of N-glycosylation may contribute to the pathogenesis of AD by impairing synaptic transmission and promoting protein aggregation. This study provides novel insights into glycosylation-dependent mechanisms of neurodegeneration, highlighting N-glycosylation as a potential therapeutic target for AD.
HostingRepository	PRIDE
AnnounceDate	2026-08-22
AnnouncementXML	Submission_2026-08-22_09:54:03.168.xml
DigitalObjectIdentifier	https://doi.org/10.6019/PXD062640
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Xing Xu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-05 09:39:49	ID requested
⏵ 1	2026-08-22 09:54:03	announced

10.6019/PXD062640;

10.1021/ACS.ANALCHEM.5C02455;

submitter keyword: glycosylation,Alzheimer’s disease, glycoproteomics, LC-MS

Ronghu wu
contact affiliation	Georgia Institute of Technology
contact email	Ronghu.wu@chemistry.gatech.edu
lab head
Xing Xu
contact affiliation	Georgia Institute of Technology
contact email	xingxu@gatech.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD062640
     1. Label: PRIDE project
     2. Name: Comprehensive and site-specific characterization of protein N-glycosylation in AD samples reveals its potential roles in protein aggregation and synaptic dysfunction