Evidence map›Paper›PMID 29859129›Full record

ArticleAlzheimer's research & therapy2018

Contactin-2, a synaptic and axonal protein, is reduced in cerebrospinal fluid and brain tissue in Alzheimer's disease.

Madhurima Chatterjee, Marta Del Campo, Tjado H J Morrema, Matthijs de Waal, Wiesje M van der Flier, Jeroen J M Hoozemans, Charlotte E Teunissen

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

Article in Alzheimer's research & therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 2 pooled it
1.4field-weighted citation impact, top 19% 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

18 citing papers in PubMed, 2 syntheses or guidelines pooled it, 29 citations in OpenAlex.

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  11. Fluid markers of synapse degeneration in synucleinopathies.Journal of neural transmission (Vienna, Austria : 1996) · 2022
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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

7 authors at 1 institution in 1 country.

Madhurima ChatterjeeNeurochemistry Laboratory, Clinical Chemistry Department, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands.ORCID 0000-0003-1647-3307
Marta Del CampoNeurochemistry Laboratory, Clinical Chemistry Department, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands.
Tjado H J MorremaDepartment of Pathology, VU University Medical Center, Amsterdam, the Netherlands.
Matthijs de WaalNeurochemistry Laboratory, Clinical Chemistry Department, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands.
Wiesje M van der FlierAlzheimer Center, VU University Medical Center, Amsterdam, the Netherlands.
Jeroen J M HoozemansDepartment of Pathology, VU University Medical Center, Amsterdam, the Netherlands.
Charlotte E TeunissenNeurochemistry Laboratory, Clinical Chemistry Department, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands. c.teunissen@vumc.nl.
Amsterdam UMC Location Vrije Universiteit Amsterdam · NL

Funding

European Neuroscience Campus Network, an Erasmus Mundus Joint Doctoral Program cycle 5/2014/P-04
6 · The paper itself

Abstract

backgroundSynaptic and axonal loss are two major mechanisms underlying Alzheimer's disease (AD) pathogenesis, and biomarkers reflecting changes in these cellular processes are needed for early diagnosis and monitoring the progression of AD. Contactin-2 is a synaptic and axonal membrane protein that interacts with proteins involved in the pathology of AD such as amyloid precursor protein (APP) and beta-secretase 1 (BACE1). We hypothesized that AD might be characterized by changes in contactin-2 levels in the cerebrospinal fluid (CSF) and brain tissue. Therefore, we aimed to investigate the levels of contactin-2 in the CSF and evaluate its relationship with disease pathology.

methodsContactin-2 was measured in CSF from two cohorts (selected from the Amsterdam Dementia Cohort), comprising samples from controls (cohort 1, n = 28; cohort 2, n = 20) and AD (cohort 1, n = 36; cohort 2, n = 70) using an analytically validated commercial enzyme-linked immunosorbent assay (ELISA). The relationship of contactin-2 with cognitive decline (Mini-Mental State Examination (MMSE)) and other CSF biomarkers reflecting AD pathology were analyzed. We further characterized the expression of contactin-2 in postmortem AD human brain (n = 14) versus nondemented controls (n = 9).

resultsCSF contactin-2 was approximately 1.3-fold reduced in AD patients compared with controls (p < 0.0001). Overall, contactin-2 levels correlated with MMSE scores (r = 0.35, p = 0.004). We observed that CSF contactin-2 correlated with the levels of phosphorylated tau within the control (r = 0.46, p < 0.05) and AD groups (r = 0.31, p < 0.05). Contactin-2 also correlated strongly with another synaptic biomarker, neurogranin (control: r = 0.62, p < 0.05; AD: r = 0.60, p < 0.01), and BACE1, a contactin-2 processing enzyme (control: r = 0.64, p < 0.01; AD: r = 0.46, p < 0.05). Results were further validated in a second cohort (p < 0.01). Immunohistochemical analysis revealed that contactin-2 is expressed in the extracellular matrix. Lower levels of contactin-2 were specifically found in and around amyloid plaques in AD hippocampus and temporal cortex.

conclusionsTaken together, these data reveal that the contactin-2 changes observed in tissues are reflected in CSF, suggesting that decreased contactin-2 CSF levels might be a biomarker reflecting synaptic or axonal loss.

Indexed as

AgedAlzheimer DiseaseAmyloid beta-PeptidesAmyloid Precursor Protein SecretasesAspartic Acid EndopeptidasesAutopsyBiomarkersBrainCohort StudiesContactin 2FemaleHumansMaleMiddle AgedNeurograninPeptide FragmentsAmyloid beta-Peptidesamyloid beta-protein (1-40)amyloid beta-protein (1-42)Amyloid Precursor Protein SecretasesAspartic Acid EndopeptidasesBACE1 protein, humanBiomarkersContactin 2NeurograninPeptide Fragmentstau ProteinsAlzheimer’s disease (AD)Beta secretase 1Contactin-2CSF biomarkerNeurograninTau

Identifiers

PMID29859129
PMCPMC5984818
OpenAlexW2806696891

What OpenQuestion holds

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LicenceCC BY
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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.