PXD060977

PXD060977 is an original dataset announced via ProteomeXchange.

Title	iTF Microglia Cell-Surface Proteomics
Description	To elucidate the impact of Aβ pathology on microglia in Alzheimer’s disease pathogenesis, we profiled the microglia surfaceome following treatment with Aβ fibrils. Our findings reveal that Aβ-associated human microglia upregulate Glypican 4 (GPC4), a GPI-anchored heparan sulfate proteoglycan (HSPG). In a Drosophila amyloidosis model, glial GPC4 expression exacerbates motor deficits and reduces lifespan, indicating that glial GPC4 contributes to a toxic cellular program during neurodegeneration. In cell culture, GPC4 enhances microglia phagocytosis of tau aggregates, and shed GPC4 can act in trans to facilitate tau aggregate uptake and seeding in neurons. Additionally, our data demonstrate that GPC4-mediated effects are amplified in the presence of APOE. These studies offer a mechanistic framework linking Aβ and tau pathology through microglial HSPGs and APOE.
HostingRepository	PRIDE
AnnounceDate	2025-09-15
AnnouncementXML	Submission_2025-09-14_19:50:04.904.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Brandon Holmes
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	timsTOF Pro 2

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-19 11:40:06	ID requested
⏵ 1	2025-09-14 19:50:12	announced

10.1186/s13024-025-00883-4;

Holmes BB, Weigel TK, Chung JM, Kaufman SK, Apresa BI, Byrnes JR, Kumru KS, Vaquer-Alicea J, Gupta A, Rose IVL, Zhang Y, Nana AL, Alter D, Grinberg LT, Spina S, Leung KK, Miller BL, Condello C, Kampmann M, Seeley WW, Coutinho-Budd JC, Wells JA, -Amyloid induces microglial expression of GPC4 and APOE leading to increased neuronal tau pathology and toxicity. Mol Neurodegener, 20(1):96(2025) [pubmed]

submitter keyword: lipopolysaccharide,iPSC Microglia, Amyloid-Beta, Surfaceomics, WGA-HRP

James A. Wells
contact affiliation	University of California San Francisco
contact email	jim.wells@ucsf.edu
lab head
Brandon Holmes
contact affiliation	UCSF
contact email	bbholmes@gmail.com
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/2025/09/PXD060977

PRIDE project URI

• PRIDE
  1. PXD060977
     1. Label: PRIDE project
     2. Name: iTF Microglia Cell-Surface Proteomics