PXD056864

PXD056864 is an original dataset announced via ProteomeXchange.

Title	Multi-omic analysis of meningeal cerebral amyloid angiopathy reveals enrichment of specific proteins and heparan sulfate disaccharides
Description	Cerebral amyloid angiopathy (CAA) is a common feature of Alzheimer’s disease in which amyloid-β (Aβ) deposits in cerebral and leptomeningeal vessel walls, predisposing to micro- and macro-hemorrhage. The vessel wall has distinct proteins and heparan sulfate (HS), linear polysaccharides that bind Aβ and promote fibril formation in vitro. Yet how vascular proteins and HS jointly associate with Aβ is unknown. Here we conducted a multi-omics study to systematically characterize the proteins as well as the HS abundance, sulfation level, and disaccharide composition of leptomeninges from 23 moderate to severe CAA cases and controls. We then analyzed the associations between Aβ and other proteins, HS, and apolipoprotein E (ApoE) genotype. We found an increase in a minor HS disaccharide, unsubstituted glucosamine, as well as 6-O sulfated disaccharides, and Aβ40 levels positively correlated with unsubstituted glucosamine. Our findings of vascular HS and protein alterations specific to CAA-affected leptomeningeal vessels provide molecular insight into the extracellular remodeling co-occurring with Aβ deposits, and provide a basis for ante-mortem diagnostic assay development and therapeutic strategies to impede Aβ - HS interaction.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-07_04:00:14.539.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Majid Ghassemian
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-16 10:27:00	ID requested
⏵ 1	2025-05-07 04:00:15	announced

10.1093/jnen/nlaf018;

Mayfield JE, Rajic AJ, Aguilar-Calvo P, Soldau K, Flores S, Lawrence R, Choudhury B, Ghassemian M, Pizzo DP, Wagner SL, Danque GA, Sumowski P, Hansen LA, Goodwill V, Esko JD, Sigurdson CJ, Multi-omic analysis of meningeal cerebral amyloid angiopathy reveals enrichment of unsubstituted glucosamine and extracellular proteins. J Neuropathol Exp Neurol, 84(5):398-411(2025) [pubmed]

ProteomeXchange project tag: Biology/Disease-Driven Human Proteome Project (B/D-HPP)

submitter keyword: human amyloid meningeal proteomics

Christina Sigurdson
contact affiliation	Department of Pathology and Medicine, University of California at San Diego, La Jolla, CA 92093, USA
contact email	csigurdson@health.ucsd.edu
lab head
Majid Ghassemian
contact affiliation	Scientist
contact email	mghassem@ucsd.edu
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/2025/05/PXD056864

PRIDE project URI

• PRIDE
  1. PXD056864
     1. Label: PRIDE project
     2. Name: Multi-omic analysis of meningeal cerebral amyloid angiopathy reveals enrichment of specific proteins and heparan sulfate disaccharides