Evidence map›Paper›PMID 27845782›Full record

ArticleTranslational psychiatry2016

A targeted proteomic multiplex CSF assay identifies increased malate dehydrogenase and other neurodegenerative biomarkers in individuals with Alzheimer's disease pathology.

R W Paterson, W E Heywood, A J Heslegrave, N K Magdalinou, U Andreasson, E Sirka, E Bliss, C F Slattery, J Toombs, J Svensson and 5 more

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

Article in Translational psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
4.5field-weighted citation impact, top 5% 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

39 citing papers in PubMed, 67 citations in OpenAlex.

  1. Context-dependent roles of osteopontin in aging-related neurological disorders.The Journal of international medical research · 2026
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  4. Current Understanding of Protein Aggregation in Neurodegenerative Diseases.International journal of molecular sciences · 2025
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  11. Osteopontin: A novel marker of pre-symptomatic sporadic Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
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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

15 authors at 5 institutions in 2 countries.

R W PatersonDementia Research Centre, Institute of Neurology, University College London, London, UK.
W E HeywoodCentre for Translational Omics, Genetics and Genomic Medicine Programme, Institute of Child Health, University College London, London, UK.
A J HeslegraveDepartment of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.
N K MagdalinouLila Weston Institute, University College London Institute of Neurology, London, UK.
U AndreassonClinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden.
E SirkaCentre for Translational Omics, Genetics and Genomic Medicine Programme, Institute of Child Health, University College London, London, UK.
E BlissCentre for Translational Omics, Genetics and Genomic Medicine Programme, Institute of Child Health, University College London, London, UK.
C F SlatteryDementia Research Centre, Institute of Neurology, University College London, London, UK.
J ToombsDepartment of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.
J SvenssonInstitute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
P JohanssonInstitute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
N C FoxDementia Research Centre, Institute of Neurology, University College London, London, UK.
H ZetterbergDepartment of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.
K MillsDementia Research Centre, Institute of Neurology, University College London, London, UK.
J M SchottDementia Research Centre, Institute of Neurology, University College London, London, UK.
University College London · GBSahlgrenska University Hospital · SEUK Dementia Research Institute · GBSkaraborg Hospital · SEUniversity of Gothenburg · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Alzheimer's disease (AD) is the most common cause of dementia. Biomarkers are required to identify individuals in the preclinical phase, explain phenotypic diversity, measure progression and estimate prognosis. The development of assays to validate candidate biomarkers is costly and time-consuming. Targeted proteomics is an attractive means of quantifying novel proteins in cerebrospinal and other fluids, and has potential to help overcome this bottleneck in biomarker development. We used a previously validated multiplexed 10-min, targeted proteomic assay to assess 54 candidate cerebrospinal fluid (CSF) biomarkers in two independent cohorts comprising individuals with neurodegenerative dementias and healthy controls. Individuals were classified as 'AD' or 'non-AD' on the basis of their CSF T-tau and amyloid Aβ1-42 profile measured using enzyme-linked immunosorbent assay; biomarkers of interest were compared using univariate and multivariate analyses. In all, 35/31 individuals in Cohort 1 and 46/36 in Cohort 2 fulfilled criteria for AD/non-AD profile CSF, respectively. After adjustment for multiple comparisons, five proteins were elevated significantly in AD CSF compared with non-AD CSF in both cohorts: malate dehydrogenase; total APOE; chitinase-3-like protein 1 (YKL-40); osteopontin and cystatin C. In an independent multivariate orthogonal projection to latent structures discriminant analysis (OPLS-DA), these proteins were also identified as major contributors to the separation between AD and non-AD in both cohorts. Independent of CSF Aβ1-42 and tau, a combination of these biomarkers differentiated AD and non-AD with an area under curve (AUC)=0.88. This targeted proteomic multiple reaction monitoring (MRM)-based assay can simultaneously and rapidly measure multiple candidate CSF biomarkers. Applying this technique to AD we demonstrate differences in proteins involved in glucose metabolism and neuroinflammation that collectively have potential clinical diagnostic utility.

Indexed as

Multiplex Polymerase Chain ReactionProteomicsAgedAlzheimer DiseaseApolipoproteins EBiomarkersChitinase-3-Like Protein 1Cohort StudiesCystatin CFemaleHumansMalate DehydrogenaseMaleMental Status ScheduleMiddle AgedNeurodegenerative DiseasesApolipoproteins EBiomarkersCHI3L1 protein, humanChitinase-3-Like Protein 1CST3 protein, humanCystatin CMalate DehydrogenaseOsteopontinSPP1 protein, human

Identifiers

PMID27845782
PMCPMC5314115
OpenAlexW2550181348

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.