Evidence map›Paper›PMID 24959687›Full record

ArticlePloS one2014

Variability of CSF Alzheimer's disease biomarkers: implications for clinical practice.

Stephanie J B Vos, Pieter Jelle Visser, Frans Verhey, Pauline Aalten, Dirk Knol, Inez Ramakers, Philip Scheltens, Marcel G M Olde Rikkert, Marcel M Verbeek, Charlotte E Teunissen

Open access · goldAbstract readMulticenter Study
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 1 pooled it
5.7field-weighted citation impact, top 3% 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

42 citing papers in PubMed, 1 synthesis or guideline pooled it, 91 citations in OpenAlex.

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  5. Agreement of cerebrospinal fluid biomarkers and amyloid-PET in a multicenter study.European archives of psychiatry and clinical neuroscience · 2025
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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

10 authors at 5 institutions in 1 country.

Stephanie J B VosDepartment of Psychiatry and Neuropsychology, Maastricht University, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht, the Netherlands.
Pieter Jelle VisserDepartment of Psychiatry and Neuropsychology, Maastricht University, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht, the Netherlands; Alzheimer center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
Frans VerheyDepartment of Psychiatry and Neuropsychology, Maastricht University, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht, the Netherlands.
Pauline AaltenDepartment of Psychiatry and Neuropsychology, Maastricht University, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht, the Netherlands.
Dirk KnolDepartment of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, the Netherlands.
Inez RamakersDepartment of Psychiatry and Neuropsychology, Maastricht University, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht, the Netherlands.
Philip ScheltensAlzheimer center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
Marcel G M Olde RikkertDepartment of Geriatric Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen and Radboud Alzheimer Centre, Nijmegen, The Netherlands.
Marcel M VerbeekDonders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen and Radboud Alzheimer Centre, Nijmegen, The Netherlands; Department of Neurology and Department of Laboratory Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Charlotte E TeunissenDepartment of Clinical Chemistry, Neurological Laboratory, VU University Medical Center, Amsterdam, The Netherlands.
Maastricht University · NLAmsterdam UMC Location VUmc · NLAmsterdam Neuroscience · NLRadboud University Medical Center · NLRadboud University Nijmegen · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCerebrospinal fluid (CSF) biomarkers are increasingly being used for diagnosis of Alzheimer's disease (AD).

objectiveWe investigated the influence of CSF intralaboratory and interlaboratory variability on diagnostic CSF-based AD classification of subjects and identified causes of this variation.

methodsWe measured CSF amyloid-β (Aβ) 1-42, total tau (t-tau), and phosphorylated tau (p-tau) by INNOTEST enzyme-linked-immunosorbent assays (ELISA) in a memory clinic population (n = 126). Samples were measured twice in a single or two laboratories that served as reference labs for CSF analyses in the Netherlands. Predefined cut-offs were used to classify CSF biomarkers as normal or abnormal/AD pattern.

resultsCSF intralaboratory variability was higher for Aβ1-42 than for t-tau and p-tau. Reanalysis led to a change in biomarker classification (normal vs. abnormal) of 26% of the subjects based on Aβ1-42, 10% based on t-tau, and 29% based on p-tau. The changes in absolute biomarker concentrations were paralleled by a similar change in levels of internal control samples between different assay lots. CSF interlaboratory variability was higher for p-tau than for Aβ1-42 and t-tau, and reanalysis led to a change in biomarker classification of 12% of the subjects based on Aβ1-42, 1% based on t-tau, and 22% based on p-tau.

conclusionsIntralaboratory and interlaboratory CSF variability frequently led to change in diagnostic CSF-based AD classification for Aβ1-42 and p-tau. Lot-to-lot variation was a major cause of intralaboratory variability. This will have implications for the use of these biomarkers in clinical practice.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesBiomarkersHumansReproducibility of Resultstau ProteinsAmyloid beta-PeptidesBiomarkerstau Proteins

Identifiers

PMID24959687
PMCPMC4069102
OpenAlexW2075606978

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.