Evidence map›Paper›PMID 31601232›Full record

ArticleJournal of neuroinflammation2019

Plasma neurofilament light chain and amyloid-β are associated with the kynurenine pathway metabolites in preclinical Alzheimer's disease.

Pratishtha Chatterjee, Henrik Zetterberg, Kathryn Goozee, Chai K Lim, Kelly R Jacobs, Nicholas J Ashton, Abdul Hye, Steve Pedrini, Hamid R Sohrabi, Tejal Shah and 8 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 43 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 2 pooled it
2.5field-weighted citation impact, top 10% 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

43 citing papers in PubMed, 2 syntheses or guidelines pooled it, 65 citations in OpenAlex.

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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

18 authors at 9 institutions in 3 countries.

Pratishtha ChatterjeeDepartment of Biomedical Sciences, Macquarie University, North Ryde, NSW, Australia.
Henrik ZetterbergDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden.
Kathryn GoozeeDepartment of Biomedical Sciences, Macquarie University, North Ryde, NSW, Australia.
Chai K LimDepartment of Biomedical Sciences, Macquarie University, North Ryde, NSW, Australia.
Kelly R JacobsDepartment of Biomedical Sciences, Macquarie University, North Ryde, NSW, Australia.
Nicholas J AshtonDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden.
Abdul HyeInstitute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Institute Clinical Neuroscience Institute, King's College London, London, UK.
Steve PedriniSchool of Medical Health and Sciences, Edith Cowan University, Joondalup, WA, Australia.
Hamid R SohrabiDepartment of Biomedical Sciences, Macquarie University, North Ryde, NSW, Australia.
Tejal ShahDepartment of Biomedical Sciences, Macquarie University, North Ryde, NSW, Australia.
Prita R AsihDepartment of Biomedical Sciences, Macquarie University, North Ryde, NSW, Australia.
Preeti DaveDepartment of Biomedical Sciences, Macquarie University, North Ryde, NSW, Australia.
Kaikai ShenAustralian eHealth Research Centre, CSIRO, Floreat, WA, Australia.
Kevin TaddeiSchool of Medical Health and Sciences, Edith Cowan University, Joondalup, WA, Australia.
David B LovejoyDepartment of Biomedical Sciences, Macquarie University, North Ryde, NSW, Australia.
Gilles J GuilleminDepartment of Biomedical Sciences, Macquarie University, North Ryde, NSW, Australia.
Kaj BlennowDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden.
Ralph N MartinsDepartment of Biomedical Sciences, Macquarie University, North Ryde, NSW, Australia. r.martins@ecu.edu.au.
Macquarie University · AUEdith Cowan University · AUAustralian Alzheimer’s Research Foundation · AUCentre for Mental Health · GBCommonwealth Scientific and Industrial Research Organisation · AUKaRaMinds · AUKing's College London · GBSahlgrenska University Hospital · SEUK Dementia Research Institute · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundBlood markers indicative of neurodegeneration (neurofilament light chain; NFL), Alzheimer's disease amyloid pathology (amyloid-β; Aβ), and neuroinflammation (kynurenine pathway; KP metabolites) have been investigated independently in neurodegenerative diseases. However, the association of these markers of neurodegeneration and AD pathology with neuroinflammation has not been investigated previously. Therefore, the current study examined whether NFL and Aβ correlate with KP metabolites in elderly individuals to provide insight on the association between blood indicators of neurodegeneration and neuroinflammation.

methodsCorrelations between KP metabolites, measured using liquid chromatography and gas chromatography coupled with mass spectrometry, and plasma NFL and Aβ concentrations, measured using single molecule array (Simoa) assays, were investigated in elderly individuals aged 65-90 years, with normal global cognition (Mini-Mental State Examination Score ≥ 26) from the Kerr Anglican Retirement Village Initiative in Ageing Health cohort.

resultsA positive correlation between NFL and the kynurenine to tryptophan ratio (K/T) reflecting indoleamine 2,3-dioxygenase activity was observed (r = .451, p < .0001). Positive correlations were also observed between NFL and kynurenine (r = .364, p < .0005), kynurenic acid (r = .384, p < .0001), 3-hydroxykynurenine (r = .246, p = .014), anthranilic acid (r = .311, p = .002), and quinolinic acid (r = .296, p = .003). Further, significant associations were observed between plasma Aβ40 and the K/T (r = .375, p < .0005), kynurenine (r = .374, p < .0005), kynurenic acid (r = .352, p < .0005), anthranilic acid (r = .381, p < .0005), and quinolinic acid (r = .352, p < .0005). Significant associations were also observed between plasma Aβ42 and the K/T ratio (r = .215, p = .034), kynurenic acid (r = .214, p = .035), anthranilic acid (r = .278, p = .006), and quinolinic acid (r = .224, p = .027) in the cohort. On stratifying participants based on their neocortical Aβ load (NAL) status, NFL correlated with KP metabolites irrespective of NAL status; however, associations between plasma Aβ and KP metabolites were only pronounced in individuals with high NAL while associations in individuals with low NAL were nearly absent.

conclusionsThe current study shows that KP metabolite changes are associated with biomarker evidence of neurodegeneration. Additionally, the association between KP metabolites and plasma Aβ seems to be NAL status dependent. Finally, the current study suggests that an association between neurodegeneration and neuroinflammation manifests in the periphery, suggesting that preventing cytoskeleton cytotoxicity by KP metabolites may have therapeutic potential.

Indexed as

AgedAged, 80 and overAlzheimer DiseaseAmyloid beta-PeptidesBiomarkersFemaleHumansKynurenineMaleNeurofilament ProteinsAmyloid beta-PeptidesBiomarkersKynurenineneurofilament protein LNeurofilament ProteinsAlzheimer’s diseaseAmyloid-betaBlood amyloid-betaBlood markersBrain amyloid-betaKynurenine pathwayNeurodegenerationNeurofilament light chainNeuroinflammation

Identifiers

PMID31601232
PMCPMC6788092
OpenAlexW2980215391

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.