Evidence map›Paper›PMID 30729296›Full record

ArticleActa neuropathologica2019

Beta-amyloid pathology in human brain microvessel extracts from the parietal cortex: relation with cerebral amyloid angiopathy and Alzheimer's disease.

Philippe Bourassa, Cyntia Tremblay, Julie A Schneider, David A Bennett, Frédéric Calon

Open access · greenAbstract read
In one paragraph

Article in Acta neuropathologica, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed, 1 pooled it
6.8field-weighted citation impact, top 2% of its field
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

46 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.

  1. The cellular model for Alzheimer's disease research: PC12 cells.Frontiers in molecular neuroscience · 2022
    Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Lower GLUT1 and unchanged MCT1 in Alzheimer's disease cerebrovasculature.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024
    Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Endothelial Dysfunction in Neurodegenerative Diseases.International journal of molecular sciences · 2023
    Review
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  18. Article
  19. Review
  20. 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

5 authors at 2 institutions in 2 countries.

Philippe BourassaFaculté de pharmacie, Université Laval, Quebec, QC, Canada.
Cyntia TremblayAxe Neurosciences, Centre de recherche du CHU de Québec-Université Laval, 2705, Boulevard Laurier, Room T2-67, Quebec, QC, G1V 4G2, Canada.
Julie A SchneiderRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
Frédéric CalonFaculté de pharmacie, Université Laval, Quebec, QC, Canada. Frederic.Calon@crchul.ulaval.ca.ORCID 0000-0002-4203-0887
Université Laval · CARush University Medical Center · US

Funding

SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI LEURGANS, SUE E. · 1991 to 2020
$49.1M
RISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4M
VHL Ubiquitin Ligase Activity and Oxygen regulated gene expressionR01CA125930 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GNARRA, JAMES R · 2007 to 2011
$1.1M
CIHR MOP 125930NCI NIH HHS R01 CA125930NIA NIH HHS P30 AG010161NIA NIH HHS R01 AG015819
6 · The paper itself

Abstract

Several pieces of evidence suggest that blood-brain barrier (BBB) dysfunction is implicated in the pathophysiology of Alzheimer's disease (AD), exemplified by the frequent occurrence of cerebral amyloid angiopathy (CAA) and the defective clearance of Aβ peptides. However, the specific role of brain microvascular cells in these anomalies remains elusive. In this study, we validated by Western, ELISA and immunofluorescence analyses a procedure to generate microvasculature-enriched fractions from frozen samples of human cerebral cortex. We then investigated Aβ and proteins involved in its clearance or production in microvessel extracts generated from the parietal cortex of 60 volunteers in the Religious Orders Study. Volunteers were categorized as AD (n = 38) or controls (n = 22) based on the ABC scoring method presented in the revised guidelines for the neuropathological diagnosis of AD. Higher ELISA-determined concentrations of vascular Aβ40 and Aβ42 were found in persons with a neuropathological diagnosis of AD, in apoE4 carriers and in participants with advanced parenchymal CAA, compared to respective age-matched controls. Vascular levels of two proteins involved in Aβ clearance, ABCB1 and neprilysin, were lower in persons with AD and positively correlated with cognitive function, while being inversely correlated to vascular Aβ40. In contrast, BACE1, a protein necessary for Aβ production, was increased in individuals with AD and in apoE4 carriers, negatively correlated to cognitive function and positively correlated to Aβ40 in microvessel extracts. The present report indicates that concentrating microvessels from frozen human brain samples facilitates the quantitative biochemical analysis of cerebrovascular dysfunction in CNS disorders. Data generated overall show that microvessels extracted from individuals with parenchymal CAA-AD contained more Aβ and BACE1 and less ABCB1 and neprilysin, evidencing a pattern of dysfunction in brain microvascular cells contributing to CAA and AD pathology and symptoms.

Indexed as

Aged, 80 and overAlzheimer DiseaseAmyloid beta-PeptidesAmyloid Precursor Protein SecretasesApolipoproteins EATP Binding Cassette Transporter, Subfamily BCerebral Amyloid AngiopathyCognitionFemaleHumansLongitudinal StudiesMaleMicrovesselsNeprilysinParietal LobeABCB1 protein, humanAmyloid beta-PeptidesAmyloid Precursor Protein SecretasesApolipoproteins EATP Binding Cassette Transporter, Subfamily BNeprilysinAlzheimer’s diseaseBeta-amyloidBlood–brain barrierBrain microvascular cellsCerebral amyloid angiopathy

Identifiers

PMID30729296
PMCPMC6483878
OpenAlexW2912784173

What OpenQuestion holds

Textmetadata
LicenceTDM
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.