Evidence map›Paper›PMID 30791945›Full record

ArticleJournal of neuroinflammation2019

Glial activation and inflammation along the Alzheimer's disease continuum.

Kaja Nordengen, Bjørn-Eivind Kirsebom, Kristi Henjum, Per Selnes, Berglind Gísladóttir, Marianne Wettergreen, Silje Bøen Torsetnes, Gøril Rolfseng Grøntvedt, Knut K Waterloo, Dag Aarsland and 2 more

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

Article in Journal of neuroinflammation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 169 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
169citing papers in PubMed, 4 pooled it
18.9field-weighted citation impact, top 1% 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

169 citing papers in PubMed, 4 syntheses or guidelines pooled it, 277 citations in OpenAlex.

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109 more citing papers are in PubMed but not listed here.

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

12 authors at 6 institutions in 2 countries.

Kaja NordengenDepartment of Neurology, Akershus University Hospital, P.B. 1000, N-1478, Lørenskog, Norway. kaja.nordengen@medisin.uio.no.ORCID http://orcid.org/0000-0002-5897-6394
Bjørn-Eivind KirsebomDepartment of Neurology, University Hospital of North Norway, Tromsø, Norway.
Kristi HenjumDepartment of Pharmacology, Institute of Clinical Medicine, University of Oslo and Oslo University Hospital, Oslo, Norway.
Per SelnesDepartment of Neurology, Akershus University Hospital, P.B. 1000, N-1478, Lørenskog, Norway.
Berglind GísladóttirDepartment of Neurology, Akershus University Hospital, P.B. 1000, N-1478, Lørenskog, Norway.
Marianne WettergreenDepartment of Neurology, Akershus University Hospital, P.B. 1000, N-1478, Lørenskog, Norway.
Silje Bøen TorsetnesDepartment of Neurology, Akershus University Hospital, P.B. 1000, N-1478, Lørenskog, Norway.
Gøril Rolfseng GrøntvedtDepartment of Neurology and Clinical Neurophysiology, University Hospital of Trondheim, Trondheim, Norway.
Knut K WaterlooDepartment of Neurology, University Hospital of North Norway, Tromsø, Norway.
Dag AarslandCentre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.
Lars N G NilssonDepartment of Pharmacology, Institute of Clinical Medicine, University of Oslo and Oslo University Hospital, Oslo, Norway.
Tormod FladbyDepartment of Neurology, Akershus University Hospital, P.B. 1000, N-1478, Lørenskog, Norway.
University of Oslo · NOAkershus University Hospital · NOOslo University Hospital · NOUniversity Hospital of North Norway · NOKing's College London · GBSt Olav's University Hospital · NO

Funding

Civitan Alzheimerfondet Not applicableHelse Sør-Øst RHF 2013131Norges Forskningsråd 217780Norges Forskningsråd 237250
6 · The paper itself

Abstract

backgroundNeuronal and glial cell interaction is essential for synaptic homeostasis and may be affected in Alzheimer's disease (AD). We measured cerebrospinal fluid (CSF) neuronal and glia markers along the AD continuum, to reveal putative protective or harmful stage-dependent patterns of activation.

methodsWe included healthy controls (n = 36) and Aβ-positive (Aβ+) cases (as defined by pathological CSF amyloid beta 1-42 (Aβ42)) with either subjective cognitive decline (SCD, n = 19), mild cognitive impairment (MCI, n = 39), or AD dementia (n = 27). The following CSF markers were measured: a microglial activation marker-soluble triggering receptor expressed on myeloid cells 2 (sTREM2), a marker of microglial inflammatory reaction-monocyte chemoattractant protein-1 (MCP-1), two astroglial activation markers-chitinase-3-like protein 1 (YKL-40) and clusterin, a neuron-microglia communication marker-fractalkine, and the CSF AD biomarkers (Aβ42, phosphorylated tau (P-tau), total tau (T-tau)). Using ANOVA with planned comparisons, or Kruskal-Wallis tests with Dunn's pairwise comparisons, CSF levels were compared between clinical groups and between stages of biomarker severity using CSF biomarkers for classification based on amyloid pathology (A), tau pathology (T), and neurodegeneration (N) giving rise to the A/T/N score.

resultsCompared to healthy controls, sTREM2 was increased in SCD (p < .01), MCI (p < .05), and AD dementia cases (p < .001) and increased in AD dementia compared to MCI cases (p < .05). MCP-1 was increased in MCI (p < .05) and AD dementia compared to both healthy controls (p < .001) and SCD cases (p < .01). YKL-40 was increased in dementia compared to healthy controls (p < .01) and MCI (p < .05). All of the CSF activation markers were increased in subjects with pathological CSF T-tau (A+T-N+ and A+T+N+), compared to subjects without neurodegeneration (A-T-N- and A+T-N-). DISCUSSION: Microglial activation as indicated by increased sTREM2 is present already at the preclinical SCD stage; increased MCP-1 and astroglial activation markers (YKL-40 and clusterin) were noted only at the MCI and AD dementia stages, respectively, and in Aβ+ cases (A+) with pathological T-tau (N+). Possible different effects of early and later glial activation need to be explored.

Indexed as

AgedAlzheimer DiseaseBiomarkersChemokine CCL2Chemokine CX3CL1Chitinase-3-Like Protein 1ClusterinCognitive DysfunctionDisease ProgressionFemaleHumansInflammationMaleMembrane GlycoproteinsNeurogliaReceptors, ImmunologicBiomarkersCCL2 protein, humanChemokine CCL2Chemokine CX3CL1CHI3L1 protein, humanChitinase-3-Like Protein 1CLU protein, humanClusterinCX3CL1 protein, humanMembrane GlycoproteinsReceptors, ImmunologicTREM2 protein, humanApolipoprotein JCerebrospinal fluidChitinase-3-like protein 1ClusterinCX3CL1Early diagnosisELISAFractalkineMCP-1MicrogliaMonocyte chemoattractant protein-1NeuroinflammationsTREM2YKL-40

Identifiers

PMID30791945
PMCPMC6383268
OpenAlexW2930060644

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.