Evidence map›Paper›PMID 36717932›Full record

ArticleAlzheimer's research & therapy2023

Decreased ratios of matrix metalloproteinases to tissue-type inhibitors in cerebrospinal fluid in sporadic and hereditary cerebral amyloid angiopathy.

Marc Vervuurt, Anna M de Kort, Lieke Jäkel, Iris Kersten, Wilson F Abdo, Floris H B M Schreuder, Ingeborg Rasing, Gisela M Terwindt, Marieke J H Wermer, Steven M Greenberg and 3 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's research & therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
2.2field-weighted citation impact, top 13% 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

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. The TIMP protein family: diverse roles in pathophysiology.American journal of physiology. Cell physiology · 2024
    Review
  8. Fluid biomarkers in cerebral amyloid angiopathy.Frontiers in neuroscience · 2024
    Review
  9. Article
  10. Review
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

13 authors at 4 institutions in 2 countries.

Marc VervuurtDepartment of Neurology, Cognition and Behaviour, Donders Institute for Brain, Radboud University Medical Center, P.O. Box 9101, 6500 HB , 830 TML, Nijmegen, The Netherlands.
Anna M de KortDepartment of Neurology, Cognition and Behaviour, Donders Institute for Brain, Radboud University Medical Center, P.O. Box 9101, 6500 HB , 830 TML, Nijmegen, The Netherlands.
Lieke JäkelDepartment of Neurology, Cognition and Behaviour, Donders Institute for Brain, Radboud University Medical Center, P.O. Box 9101, 6500 HB , 830 TML, Nijmegen, The Netherlands.
Iris KerstenDepartment of Neurology, Cognition and Behaviour, Donders Institute for Brain, Radboud University Medical Center, P.O. Box 9101, 6500 HB , 830 TML, Nijmegen, The Netherlands.
Wilson F AbdoDepartment of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
Floris H B M SchreuderDepartment of Neurology, Cognition and Behaviour, Donders Institute for Brain, Radboud University Medical Center, P.O. Box 9101, 6500 HB , 830 TML, Nijmegen, The Netherlands.
Ingeborg RasingDepartment of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
Gisela M TerwindtDepartment of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
Marieke J H WermerDepartment of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
Steven M GreenbergDepartment of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Catharina J M KlijnDepartment of Neurology, Cognition and Behaviour, Donders Institute for Brain, Radboud University Medical Center, P.O. Box 9101, 6500 HB , 830 TML, Nijmegen, The Netherlands.
H Bea KuiperijDepartment of Neurology, Cognition and Behaviour, Donders Institute for Brain, Radboud University Medical Center, P.O. Box 9101, 6500 HB , 830 TML, Nijmegen, The Netherlands.
Marcel M VerbeekDepartment of Neurology, Cognition and Behaviour, Donders Institute for Brain, Radboud University Medical Center, P.O. Box 9101, 6500 HB , 830 TML, Nijmegen, The Netherlands. Marcel.Verbeek@radboudumc.nl.
Radboud University Nijmegen · NLLeiden University Medical Center · NLRadboud University Medical Center · NLMassachusetts General Hospital · US

Funding

Cerebral amyloid angiopathy fluid biomarkers evaluation (CAFE)R01NS104147 · NINDS · UNIVERSITY OF RHODE ISLAND · PI VAN NOSTRAND, WILLIAM E. · 2018 to 2022
$3.2M
NINDS NIH HHS R01 NS104147
6 · The paper itself

Abstract

backgroundTo evaluate the potential of cerebrospinal fluid (CSF) levels of matrix metalloproteinases and tissue-type inhibitors (MMP; TIMP), and ratios of MMPs to TIMPs, to function as biomarkers for sporadic or hereditary cerebral amyloid angiopathy (CAA).

methodsCSF concentrations of the matrix metalloproteinases MMP-2, MMP-9 and MMP-14, as well as the tissue inhibitors of metalloproteinases TIMP-1, TIMP-2 and TIMP-3, were determined using immunoassays. These assays were applied to two, independent study groups of sporadic CAA (sCAA) (n = 28/43) and control subjects (n = 40/40), as well as to groups of pre-symptomatic (n = 11) and symptomatic hereditary Dutch-CAA (D-CAA) patients (n = 12), and age-matched controls (n = 22/28, respectively).

resultsIn the sCAA/control cohorts, inconsistent differences were found for individual MMPs and TIMPs, but MMP-2/TIMP-2 (discovery/validation: p = 0.004; p = 0.02) and MMP-14/TIMP-2 ratios (discovery/validation: p < 0.001; p = 0.04) were consistently decreased in sCAA, compared to controls. Moreover, MMP-14 was decreased in symptomatic D-CAA (p = 0.03), compared to controls. The MMP-14/TIMP-1 (p = 0.03) and MMP-14/TIMP-2 (p = 0.04) ratios were decreased in symptomatic D-CAA compared to controls and also compared to pre-symptomatic D-CAA (p = 0.004; p = 0.005, respectively).

conclusionCSF MMP-2/TIMP-2 and MMP-14/TIMP-2 were consistently decreased in sCAA, compared to controls. Additionally, MMP-14/TIMP-2 levels were also decreased in symptomatic D-CAA, compared to both pre-symptomatic D-CAA and controls, and can therefore be considered a biomarker for sporadic and late-stage hereditary forms of CAA.

Indexed as

Cerebral Amyloid Angiopathy, FamilialTissue Inhibitor of Metalloproteinase-2HumansMatrix Metalloproteinase 14Matrix Metalloproteinase 2Tissue Inhibitor of Metalloproteinase-1Matrix Metalloproteinase 14Matrix Metalloproteinase 2Tissue Inhibitor of Metalloproteinase-1Tissue Inhibitor of Metalloproteinase-2BiomarkersHereditary cerebral amyloid angiopathy cerebrospinal fluidMatrix metalloproteinasesSporadic cerebral amyloid angiopathyTissue inhibitors of matrix metalloproteinases

Identifiers

PMID36717932
PMCPMC9885599
OpenAlexW4318476746

What OpenQuestion holds

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Registered trials

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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.