Evidence map›Paper›PMID 37279935›Full record

ArticleClinical chemistry2023

Metrologically Traceable Quantification of 3 Apolipoprotein E Isoforms in Cerebrospinal Fluid.

Huu-Hien Huynh, Kellie Kuch, Allen Orquillas, Katrina Forrest, Lili Barahona-Carrillo, Dirk Keene, Victor W Henderson, Anthony D Wagner, Kathleen L Poston, Thomas J Montine and 5 more

Open access · greenAbstract read
In one paragraph

Article in Clinical chemistry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

9 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Performance of novel tau antibodies across multiple modalities for Alzheimer's disease assessment.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  6. Article
  7. Article
  8. Article
  9. Clinical Proteomics for Solid Organ Tissues.Molecular & cellular proteomics : MCP · 2023
    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

15 authors at 2 institutions in 1 country.

Huu-Hien HuynhDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, United States.ORCID 0000-0002-7814-3189
Kellie KuchDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, United States.
Allen OrquillasDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, United States.
Katrina ForrestDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, United States.
Lili Barahona-CarrilloDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, United States.
Dirk KeeneDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, United States.
Victor W HendersonDepartment of Epidemiology and Population Health, Stanford University, Stanford, CA, United States.
Anthony D WagnerDepartment of Psychology, Stanford University, Stanford, CA, United States.
Kathleen L PostonDepartment of Neurology and Neurological Science, Stanford University School of Medicine, Stanford, CA, United States.
Thomas J MontineDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, United States.
Amy LinDepartment of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, United States.
Lu TianDepartment of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, United States.
Michael J MacCossDepartment of Genome Sciences, University of Washington, Seattle, WA, United States.
Michelle A EmrickDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, United States.
Andrew N HoofnagleDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, United States.ORCID 0000-0002-6449-0243
University of Washington · USStanford University · US

Funding

Translational pharmacoepidemiology: neuroprotection and neurotoxicity of antihypertensives and strong anticholinergicsU19AG066567 · NIA · KAISER FOUNDATION RESEARCH INSTITUTE · PI CHRISTOPHER DIRK KEENE · 2021 to 2026
$80.4M
University of Washington Alzheimer's Disease Research CenterP30AG066509 · NIA · UNIVERSITY OF WASHINGTON · PI ALI SHOJAIE · 2020 to 2026
$29.0M
Stanford Alzheimer's Disease Research CenterAdmin Supp: Developing iPSC models for AD and PDP30AG066515 · NIA · STANFORD UNIVERSITY · PI ELIZABETH MORMINO · 2020 to 2026
$29.0M
Udall Center Director's meeting poster awardP50NS062684 · NINDS · UNIVERSITY OF WASHINGTON · PI MONTINE, THOMAS J · 2009 to 2020
$18.3M
Project 4: Novel reagent development to enable molecular characterizationU19AG065156 · NIA · UNIVERSITY OF WASHINGTON · PI BAKER, DAVID · 2020 to 2024
$15.9M
Working Memory in Parkinson Disease: A Cognitive & Systems Neuroscience ApproachP50AG047366 · NIA · STANFORD UNIVERSITY · PI GREICIUS, MICHAEL D · 2015 to 2019
$7.9M
Hippocampal-dependent memory decline in aging and early Alzheimer's diseaseR01AG074339 · NIA · STANFORD UNIVERSITY · PI ELIZABETH MORMINO · 2022 to 2026
$6.0M
The impact of early Tau pathology on cognitive progression and neuropsychiatric symptoms in Parkinson's diseaseR01NS115114 · NINDS · STANFORD UNIVERSITY · PI ANDREASSON, KATRIN I., POSTON, KATHLEEN LOMBARD · 2019 to 2023
$4.2M
Effects of attention and goal-state lapses on memory in healthy and pathological agingR01AG065255 · NIA · STANFORD UNIVERSITY · PI WAGNER, ANTHONY D · 2020 to 2024
$3.7M
High-resolution imaging of hippocampal mechanisms in age-related memory decline.R01AG048076 · NIA · STANFORD UNIVERSITY · PI WAGNER, ANTHONY D · 2014 to 2018
$1.9M
Multi-modal Study of Cognitive and Neural Differences in Media MultitaskersR56MH111672 · NIMH · STANFORD UNIVERSITY · PI ANGUERA, JOAQUIN A, WAGNER, ANTHONY D · 2017 to 2018
$1.2M
Basal Ganglia Modulation of Cognitive Systems in Parkinson's diseaseK23NS075097 · NINDS · STANFORD UNIVERSITY · PI POSTON, KATHLEEN LOMBARD · 2011 to 2015
$936k
NIA NIH HHS P30 AG066509NIA NIH HHS P30 AG066515NIA NIH HHS P50 AG047366NIA NIH HHS R01 AG048076NIA NIH HHS R01 AG065255NIA NIH HHS R01 AG074339NIA NIH HHS R21 AG058111NIA NIH HHS R21 AG058859NIA NIH HHS U19 AG065156NIA NIH HHS U19 AG066567NIMH NIH HHS R56 MH111672NINDS NIH HHS K23 NS075097NINDS NIH HHS P50 NS062684NINDS NIH HHS R01 NS115114NINDS NIH HHS R21 NS113024
6 · The paper itself

Abstract

backgroundAPOE genotype is associated with Alzheimer disease. Thus, the concentration of apolipoprotein E (apoE) isoforms in cerebrospinal fluid (CSF) could be altered in dementia. However, conflicting results have been obtained in different studies. Carefully validated and standardized assays could improve the interpretation of research findings, allow their replication in other laboratories, and generalize their application.

methodsTo evaluate this hypothesis, we aimed to develop, validate, and standardize a new measurement procedure using LC-MS/MS. Purified recombinant apoE protein standards (E2, E3, E4) were thoroughly characterized and used to assign the concentration of a matrix-matched calibration material that contained each apoE isoform, which ensured the metrological traceability of results.

resultsThe assay of each isoform in human CSF was precise (≤11%CV) and of moderate throughput (approximately 80 samples per day). It demonstrated good linearity and parallelism for lumbar CSF, ventricular CSF, and bovine CSF. The use of an SI-traceable matrix-matched calibrator enabled precise and accurate measurements. There was no association observed between total apoE concentration and the number of Ɛ4 alleles in a cohort of 322 participants. However, the concentration of each isoform was significantly different in heterozygotes, with E4 > E3 > E2. Isoform concentrations were associated with cognitive and motor symptoms but contributed negligibly to a predictive model of cognitive impairment that included established CSF biomarkers.

conclusionsOur method simultaneously measures each apoE isoform in human CSF with excellent precision and accuracy. A secondary matrix-matched material has been developed and is available to other laboratories to improve interlaboratory agreement.

Indexed as

Alzheimer DiseaseApolipoprotein E4Amyloid beta-PeptidesAnimalsApolipoproteins ECattleChromatography, LiquidHumansProtein IsoformsTandem Mass SpectrometryAmyloid beta-PeptidesApolipoprotein E4Apolipoproteins EProtein Isoforms

Identifiers

PMID37279935
PMCPMC10320014
OpenAlexW4379598903

What OpenQuestion holds

Textmetadata
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.