Evidence map›Paper›PMID 40156913›Full record

ArticleJournal of neuropathology and experimental neurology2025

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

Joshua E Mayfield, Alexander J Rajic, Patricia Aguilar-Calvo, Katrin Soldau, Samantha Flores, Roger Lawrence, Biwsa Choudhury, Majid Ghassemian, Donald P Pizzo, Steven L Wagner and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neuropathology and experimental neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Joshua E MayfieldDepartment of Pathology, University of California, San Diego, La Jolla, CA, United States.
Alexander J RajicDepartment of Pathology, University of California, San Diego, La Jolla, CA, United States.
Patricia Aguilar-CalvoDepartment of Pathology, University of California, San Diego, La Jolla, CA, United States.
Katrin SoldauDepartment of Pathology, University of California, San Diego, La Jolla, CA, United States.
Samantha FloresDepartment of Pathology, University of California, San Diego, La Jolla, CA, United States.
Roger LawrenceDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, United States.
Biwsa ChoudhuryDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, United States.
Majid GhassemianDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, United States.
Donald P PizzoDepartment of Pathology, University of California, San Diego, La Jolla, CA, United States.
Steven L WagnerDepartment of Neurosciences, University of California, San Diego, La Jolla, CA, United States.
Garrett A DanqueDepartment of Pathology, University of California, San Diego, La Jolla, CA, United States.
Paige SumowskiDepartment of Pathology, University of California, San Diego, La Jolla, CA, United States.
Lawrence A HansenDepartment of Pathology, University of California, San Diego, La Jolla, CA, United States.
Vanessa GoodwillDepartment of Pathology, University of California, San Diego, La Jolla, CA, United States.
Jeffery D EskoDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, United States.
Christina J SigurdsonDepartment of Pathology, University of California, San Diego, La Jolla, CA, United States.

Funding

UCSD Shiley-Marcos Alzheimer's Disease Research Center P30P30AG062429 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DOUGLAS R GALASKO · 2019 to 2026
$34.9M
Siglec Modulation of Inflammatory ResponsesP01HL107150 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI VARKI, AJIT P · 2011 to 2017
$18.0M
Mechanisms of Prion Aggregation and Species BarriersR01NS069566 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ESKO, JEFFREY D, RAVITS, JOHN · 2011 to 2025
$5.7M
Mechanisms of Prion SpreadR01NS076896 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SIGURDSON, CHRISTINA · 2012 to 2021
$3.4M
Structure and Function of 3-O-sulfation in Heparan SulfateR01GM093131 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ESKO, JEFFREY D · 2010 to 2013
$1.2M
Probing prion clearance through interstitial fluid and perivascular pathwaysR21NS110409 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SIGURDSON, CHRISTINA · 2018 to 2019
$433k
Role of heparan sulfate in neural cell vulnerability to prionsK99AG061251 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI AGUILAR CALVO, PATRICIA · 2019 to 2021
$375k
NHLBI NIH HHS P01 HL107150NIA NIH HHS K99 AG061251NIA NIH HHS P30 AG062429NIGMS NIH HHS R01 GM093131NIH HHS NS069566NINDS NIH HHS R01 NS069566NINDS NIH HHS R01 NS076896NINDS NIH HHS R21 NS110409
6 · The paper itself

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 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 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 genotype. We found an increase in a minor HS disaccharide containing unsubstituted glucosamine, as well as 6-O sulfated disaccharides; Aβ40 levels positively correlated with unsubstituted glucosamine. There was also an increase in extracellular proteins derived from brain parenchyma or plasma, including olfactomedin-like protein 3, fibrinogen, serum amyloid protein, apolipoprotein E, and secreted frizzled related protein-3. Our findings of vascular HS and protein alterations specific to CAA-affected leptomeningeal vessels provide molecular insight into the extracellular remodeling that co-occurs with Aβ deposits and may indicate a basis for antemortem diagnostic assay development and therapeutic strategies to impede Aβ-HS interactions.

Indexed as

Cerebral Amyloid AngiopathyGlucosamineMeningesAgedAged, 80 and overAmyloid beta-PeptidesApolipoproteins EFemaleHeparan SulfateHumansMaleMiddle AgedMultiomicsProteomicsAmyloid beta-PeptidesApolipoproteins EGlucosamineHeparan SulfateAlzheimer's diseaseglycomicsheparan sulfateneurodegenerationprotein misfoldingproteomics

Identifiers

PMID40156913
PMCPMC12012350

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.