Evidence map›Paper›PMID 31985466›Full record

ArticleJournal of Alzheimer's disease : JAD2020

Validation of Plasma Proteomic Biomarkers Relating to Brain Amyloid Burden in the EMIF-Alzheimer's Disease Multimodal Biomarker Discovery Cohort.

Sarah Westwood, Alison L Baird, Sneha N Anand, Alejo J Nevado-Holgado, Andrey Kormilitzin, Liu Shi, Abdul Hye, Nicholas J Ashton, Angharad R Morgan, Isabelle Bos and 40 more

Abstract readMulticenter StudyValidation Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of Alzheimer's disease : JAD, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
–field-weighted citation impact
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

14 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Blood DNA methylomic signatures associated with CSF biomarkers of Alzheimer's disease in the EMIF-AD study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
    Article
  5. Review
  6. Artificial intelligence for dementia-Applied models and digital health.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023
    Review
  7. A Perspective: Challenges in Dementia Research.Medicina (Kaunas, Lithuania) · 2022
    Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Article
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

50 authors.

Sarah WestwoodDepartment of Psychiatry, University of Oxford, UK.
Alison L BairdDepartment of Psychiatry, University of Oxford, UK.
Sneha N AnandDepartment of Psychiatry, University of Oxford, UK.
Alejo J Nevado-HolgadoDepartment of Psychiatry, University of Oxford, UK.
Andrey KormilitzinDepartment of Psychiatry, University of Oxford, UK.
Liu ShiDepartment of Psychiatry, University of Oxford, UK.
Abdul HyeMaurice Wohl Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK.
Nicholas J AshtonMaurice Wohl Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK.
Angharad R MorganDementia Research Institute Cardiff, Cardiff University, Cardiff, UK.
Isabelle BosDepartment of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands.
Stephanie J B VosDepartment of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands.
Susan BakerJanssen R&D, Titusville, NJ, USA.
Noel J BuckleyDepartment of Psychiatry, University of Oxford, UK.
Mara Ten KateAlzheimer Center, VU University Medical Center, Amsterdam, the Netherlands.
Philip ScheltensAlzheimer Center, VU University Medical Center, Amsterdam, the Netherlands.
Charlotte E TeunissenAlzheimer Center, VU University Medical Center, Amsterdam, the Netherlands.
Rik VandenbergheUniversity Hospital Leuven, Leuven, Belgium.
Silvy GabelUniversity Hospital Leuven, Leuven, Belgium.
Karen MeersmansUniversity Hospital Leuven, Leuven, Belgium.
Sebastiaan EngelborghsDepartment of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, University of Antwerp, Antwerp, Belgium.
Ellen E De RoeckDepartment of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, University of Antwerp, Antwerp, Belgium.
Kristel SleegersCenter for Neurosciences, Vrije Universiteit Brussel (VUB), Brussels, Belgium.
Giovanni B FrisoniUniversity of Geneva, Geneva, Switzerland.
Olivier BlinAIX Marseille University, INS, Ap-Hm, Marseille, France.
Jill C RichardsonNeurosciences Therapeutic Area, GlaxoSmithKline R&D, Stevenage, UK.
Régis BordetUniversity of Lille, Inserm, CHU Lille, France.
José L MolinuevoAlzheimer's Disease & Other Cognitive Disorders Unit, Hopsital Clínic-IDIBAPS, Barcelona, Spain.
Lorena RamiBarcelona Beta Brain Research Center, Unversitat Pompeu Fabra, Barcelona, Spain.
Anders WallinInstitute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Petronella KettunenInstitute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Magda Tsolaki1st Department of Neurology, AHEPA University Hospital, Makedonia, Thessaloniki, Greece.
Frans VerheyDepartment of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands.
Alberto LléoHospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Isabel SalaDepartment of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Julius PoppUniversity Hospital of Lausanne, Lausanne, Switzerland.
Gwendoline PeyratoutUniversity Hospital of Lausanne, Lausanne, Switzerland.
Pablo Martinez-LageGeriatric Psychiatry, Department of Mental Health and Psychiatry, Geneva University Hospitals, Geneva, Switzerland.
Mikel TaintaCITA-Alzheimer Foundation, San Sebastian, Spain.
Peter JohannsenDanish Dementia Research Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Yvonne Freund-LeviDepartment of Neurobiology, Caring Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, and Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Lutz FrölichDepartment of Geriatric Psychiatry, Zentralinstitut für Seelische Gesundheit, University of Heidelberg, Mannheim, Germany.
Valerija DobricicLübeck Interdisciplinary Platform for Genome Analytics, Institutes of Neurogenetics and Cardiogenetics, University of Lübeck, Lübeck, Germany.
Cristina Legido-QuigleyKings College London, London, UK.
Lars BertramLübeck Interdisciplinary Platform for Genome Analytics, Institutes of Neurogenetics and Cardiogenetics, University of Lübeck, Lübeck, Germany.
Frederik BarkhofDepartment of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherland.
Henrik ZetterbergDepartment of Psychiatry and Neurochemistry, University of Gothenburg, Mölndal, Sweden.
B Paul MorganDementia Research Institute Cardiff, Cardiff University, Cardiff, UK.
Johannes StrefferCenter for Neurosciences, Vrije Universiteit Brussel (VUB), Brussels, Belgium.
Pieter Jelle VisserDepartment of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands.
Simon LovestoneDepartment of Psychiatry, University of Oxford, UK.

Funding

Department of HealthMedical Research Council MC_PC_17215Medical Research Council MR/L023784/2Wellcome TrustWellcome Trust 104025/Z/14/Z
6 · The paper itself

Abstract

We have previously investigated, discovered, and replicated plasma protein biomarkers for use to triage potential trials participants for PET or cerebrospinal fluid measures of Alzheimer's disease (AD) pathology. This study sought to undertake validation of these candidate plasma biomarkers in a large, multi-center sample collection. Targeted plasma analyses of 34 proteins with prior evidence for prediction of in vivo pathology were conducted in up to 1,000 samples from cognitively healthy elderly individuals, people with mild cognitive impairment, and in patients with AD-type dementia, selected from the EMIF-AD catalogue. Proteins were measured using Luminex xMAP, ELISA, and Meso Scale Discovery assays. Seven proteins replicated in their ability to predict in vivo amyloid pathology. These proteins form a biomarker panel that, along with age, could significantly discriminate between individuals with high and low amyloid pathology with an area under the curve of 0.74. The performance of this biomarker panel remained consistent when tested in apolipoprotein E ɛ4 non-carrier individuals only. This blood-based panel is biologically relevant, measurable using practical immunocapture arrays, and could significantly reduce the cost incurred to clinical trials through screen failure.

Indexed as

ProteomicsAgedAlzheimer DiseaseApolipoprotein E4BiomarkersBlood ProteinsBody BurdenCerebral Amyloid AngiopathyCognitive DysfunctionCohort StudiesFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedPositron-Emission TomographyApolipoprotein E4BiomarkersBlood ProteinsMAPT protein, humantau ProteinsAlzheimer’s diseaseamyloid-βbiomarkersplasmaproteomics

Identifiers

PMID31985466
PMCPMC7175945

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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.