Dataset Information

Multi-omic analysis of meningeal cerebral amyloid angiopathy reveals enrichment of specific proteins and heparan sulfate disaccharides

ABSTRACT: 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.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain

SUBMITTER: Majid Ghassemian

LAB HEAD: Christina Sigurdson

PROVIDER: PXD056864 | Pride | 2025-05-07

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	4981.protein-peptides.csv	Csv
	4986.protein-peptides.csv	Csv
	5111.protein-peptides.csv	Csv
	5248.protein-peptides.csv	Csv
	5302.protein-peptides.csv	Csv

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Publications

Multi-omic analysis of meningeal cerebral amyloid angiopathy reveals enrichment of unsubstituted glucosamine and extracellular proteins.

Mayfield Joshua E JE Rajic Alexander J AJ Aguilar-Calvo Patricia P Soldau Katrin K Flores Samantha S Lawrence Roger R Choudhury Biwsa B Ghassemian Majid M Pizzo Donald P DP Wagner Steven L SL Danque Garrett A GA Sumowski Paige P Hansen Lawrence A LA Goodwill Vanessa V Esko Jeffery D JD Sigurdson Christina J CJ

Journal of neuropathology and experimental neurology 20250501 5

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 vessels to micro- and macro-hemorrhages. The vessel walls contain distinct proteins and heparan sulfate (HS), yet how vascular proteins and HS jointly associate with Aβ is unknown. We conducted the first multi-omics study to systematically characterize the proteins as well as the HS abundance, sulfation level, and disaccharide com ...[more]

PMID: 40156913

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