Evidence map›Paper›PMID 35081972›Full record

ArticleProteome science2022

Analysis of plasma proteins using 2D gels and novel fluorescent probes: in search of blood based biomarkers for Alzheimer's disease.

Scott B Laffoon, James D Doecke, Anne M Roberts, Jennifer A Vance, Benjamin D Reeves, Kelly K Pertile, Rebecca L Rumble, Chris J Fowler, Brett Trounson, David Ames and 6 more

Open access · goldAbstract read
In one paragraph

Article in Proteome science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.1field-weighted citation impact, top 27% 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

7 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Article
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  4. Review
  5. Review
  6. Discovery of a Missense Mutation (Q222K) of theJournal of Alzheimer's disease reports · 2023
    Article
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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

16 authors at 6 institutions in 2 countries.

Scott B LaffoonFlorey Institute of Neuroscience and Mental Health and The University of Melbourne Dementia Research Centre, Parkville, VIC, 3010, Australia.
James D DoeckeAustralian e-Health Research Centre, CSIRO and Cooperative Research Centre of Mental Health, Royal Brisbane and Women's Hospital, Brisbane, QLD, 4029, Australia.
Anne M RobertsDepartment of Biochemistry, Emory School of Medicine, 4001 Rollins Research Building, Atlanta, GA, 30322, USA.
Jennifer A VanceAIT Bioscience, 7840 Innovation Blvd., Indianapolis, IN, 46278, USA.
Benjamin D ReevesDepartment of Chemistry and Biochemistry, Montana State University, Bozeman, MT, 59715, USA.
Kelly K PertileFlorey Institute of Neuroscience and Mental Health and The University of Melbourne Dementia Research Centre, Parkville, VIC, 3010, Australia.
Rebecca L RumbleFlorey Institute of Neuroscience and Mental Health and The University of Melbourne Dementia Research Centre, Parkville, VIC, 3010, Australia.
Chris J FowlerFlorey Institute of Neuroscience and Mental Health and The University of Melbourne Dementia Research Centre, Parkville, VIC, 3010, Australia.
Brett TrounsonFlorey Institute of Neuroscience and Mental Health and The University of Melbourne Dementia Research Centre, Parkville, VIC, 3010, Australia.
David AmesFlorey Institute of Neuroscience and Mental Health and The University of Melbourne Dementia Research Centre, Parkville, VIC, 3010, Australia.
Ralph MartinsCooperative Research Centre for Mental Health, Carlton South, VIC, Australia.
Ashley I BushFlorey Institute of Neuroscience and Mental Health and The University of Melbourne Dementia Research Centre, Parkville, VIC, 3010, Australia.
Colin L MastersFlorey Institute of Neuroscience and Mental Health and The University of Melbourne Dementia Research Centre, Parkville, VIC, 3010, Australia.
Paul A GriecoDepartment of Chemistry and Biochemistry, Montana State University, Bozeman, MT, 59715, USA.
Edward A DratzDepartment of Chemistry and Biochemistry, Montana State University, Bozeman, MT, 59715, USA.
Blaine R RobertsDepartment of Biochemistry, Emory School of Medicine, 4001 Rollins Research Building, Atlanta, GA, 30322, USA. blaine.roberts@emory.edu.ORCID http://orcid.org/0000-0001-5466-0053
The University of Melbourne · AUMontana State University · USEmory University · USCommonwealth Scientific and Industrial Research Organisation · AUEdith Cowan University · AUIndiana Biosciences Research Institute · US

Funding

SYSTEMS BIOLOGY OF HOST-PATHOGEN INTERACTIONSP20RR024237 · NCRR · MONTANA STATE UNIVERSITY - BOZEMAN · PI GAUSS, KATHERINE A. · 2008 to 2011
$8.1M
Multiplex Fluorescent Dyes for Ultrasensitive ProteomicsR42RR021790 · NCRR · ZDYE, LLC · PI DRATZ, EDWARD A · 2008 to 2010
$1.1M
NCRR NIH HHS P20 RR024237NCRR NIH HHS R42 RR021790NIH HHS 1P20RR024237NIH HHS 5R42RR021790
6 · The paper itself

Abstract

backgroundThe Australian Imaging and Biomarker Lifestyle (AIBL) study of aging is designed to aid the discovery of biomarkers. The current study aimed to discover differentially expressed plasma proteins that could yield a blood-based screening tool for Alzheimer's disease.

methodsThe concentration of proteins in plasma covers a vast range of 12 orders of magnitude. Therefore, to search for medium to low abundant biomarkers and elucidate mechanisms of AD, we immuno-depleted the most abundant plasma proteins and pre-fractionated the remaining proteins by HPLC, prior to two-dimensional gel electrophoresis. The relative levels of approximately 3400 protein species resolved on the 2D gels were compared using in-gel differential analysis with spectrally resolved fluorescent protein detection dyes (Zdyes™). Here we report on analysis of pooled plasma samples from an initial screen of a sex-matched cohort of 72 probable AD patients and 72 healthy controls from the baseline time point of AIBL.

resultsWe report significant changes in variants of apolipoprotein E, haptoglobin, α1 anti-trypsin, inter-α trypsin inhibitor, histidine-rich glycoprotein, and a protein of unknown identity. α1 anti-trypsin and α1 anti-chymotrypsin demonstrated plasma concentrations that were dependent on APOE ε4 allele dose. Our analysis also identified an association with the level of Vitamin D binding protein fragments and complement factor I with sex. We then conducted a preliminary validation study, on unique individual samples compared to the discovery cohort, using a targeted LC-MS/MS assay on a subset of discovered biomarkers. We found that targets that displayed a high degree of isoform specific changes in the 2D gels were not changed in the targeted MS assay which reports on the total level of the biomarker.

conclusionsThis demonstrates that further development of mass spectrometry assays is needed to capture the isoform complexity that exists in theses biological samples. However, this study indicates that a peripheral protein signature has potential to aid in the characterization of AD.

Indexed as

2D-PAGEAlzheimer’s diseaseAPOEBiomarkersBloodPlasmaProteomicsZdye

Identifiers

PMID35081972
PMCPMC8790928
OpenAlexW4210309921

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.