Evidence map›Paper›PMID 27112350›Full record

ArticleMolecular neurodegeneration2016

Network-driven plasma proteomics expose molecular changes in the Alzheimer's brain.

Philipp A Jaeger, Kurt M Lucin, Markus Britschgi, Badri Vardarajan, Ruo-Pan Huang, Elizabeth D Kirby, Rachelle Abbey, Bradley F Boeve, Adam L Boxer, Lindsay A Farrer and 20 more

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

Article in Molecular neurodegeneration, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
3.7field-weighted citation impact, top 7% 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

23 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
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  3. Protein Microarray Analysis with GenePix.Methods in molecular biology (Clifton, N.J.) · 2025
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  9. Phage Microarrays for Screening of Humoral Immune Responses.Methods in molecular biology (Clifton, N.J.) · 2021
    Article
  10. Article
  11. Protein Microarrays for Ocular Diseases.Methods in molecular biology (Clifton, N.J.) · 2021
    Review
  12. Article
  13. Review
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  15. Article
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  17. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

30 authors at 14 institutions in 4 countries.

Philipp A JaegerDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA. pjaeger@ucsd.edu.
Kurt M LucinDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Markus BritschgiDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Badri VardarajanDepartment of Medicine (Biomedical Genetics), Boston University Schools of Medicine, Boston, MA, USA.
Ruo-Pan HuangRayBiotech, Guangzhou, China.
Elizabeth D KirbyDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Rachelle AbbeyDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Bradley F BoeveDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
Adam L BoxerDepartment of Neurology, University of California San Francisco, San Francisco, CA, USA.
Lindsay A FarrerDepartment of Medicine (Biomedical Genetics), Boston University Schools of Medicine, Boston, MA, USA.
NiCole FinchDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Neill R Graff-RadfordDepartment of Neurology, Mayo Clinic, Jacksonville, FL, USA.
Elizabeth HeadDepartments of Pharmacology and Nutritional Sciences and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
Matan HofreeDepartment of Computer Science and Engineering, University of California San Diego, La Jolla, CA, USA.
Ruochun HuangRayBiotech, Guangzhou, China.
Hudson JohnsDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Anna KarydasDepartment of Neurology, University of California San Francisco, San Francisco, CA, USA.
David S KnopmanDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
Andrey LobodaGenetics and Pharmacogenomics, Merck Research Laboratories, West Point, PA, USA.
Eliezer MasliahDepartment of Pathology, University of California San Diego, La Jolla, CA, USA.
Ramya NarasimhanDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Ronald C PetersenDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
Alexei PodtelezhnikovGenetics and Pharmacogenomics, Merck Research Laboratories, West Point, PA, USA.
Suraj PradhanDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Rosa RademakersDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Chung-Huan SunDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Steven G YounkinDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Bruce L MillerDepartment of Neurology, University of California San Francisco, San Francisco, CA, USA.
Trey IdekerDepartments of Bioengineering and Medicine, University of California San Diego, La Jolla, CA, USA.
Tony Wyss-CorayDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA. twc@stanford.edu.
Stanford University · USMayo Clinic in Florida · USMayo Clinic in Arizona · USUniversity of California San Diego · USUniversity of California, San Francisco · USBoston University · USUnited States Military Academy · USEastern Connecticut State University · USLa Jolla Bioengineering Institute · USRayBiotech (China) · CNRayBiotech (United States) · USRoche (Switzerland) · CHStanford Medicine · USUniversity of Kentucky · US

Funding

TDP-43 Loss-of-Function: Biology to BiomarkersP01AG019724 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Jennifer Merrilees · 2002 to 2026
$67.2M
VIRUS-INDUCED BRAIN PATHOLOGYP50AG005131 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BREWER, JAMES B · 1985 to 2018
$55.4M
SUPPLEMENT TO ALZHEIMERS DISEASE PATIENT REGISTRYU01AG006786 · NIA · MAYO CLINIC ROCHESTER · PI GRAFF-RADFORD, JONATHAN, JACK, CLIFFORD R. · 1986 to 2023
$49.6M
Therapeutics Core (Page 286)P30MH062261 · NIMH · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI GENDELMAN, HOWARD E · 2000 to 2021
$37.7M
UC Irvine Alzheimer's Disease Research Center Induced Pluripotent Stem Cell CoreP50AG016573 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI LAFERLA, FRANK M · 2000 to 2019
$37.0M
THE PGRN/TDP-43 AXIS IN ALZHEIMER?S DISEASE AND NEURODEGENERATIONP50AG016574 · NIA · MAYO CLINIC ROCHESTER · PI BU, GUOJUN · 1999 to 2018
$36.9M
PrPSc SPECIFIC INTERACTION WITH NOVEL PrP-Fc FUSION PROTEINSP50AG023501 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MILLER, BRUCE L · 2004 to 2018
$27.1M
The Four Repeat Tauopathy Neuroimaging InitiativeR01AG038791 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BOXER, ADAM L. · 2010 to 2020
$18.1M
TR&D 3 - Network Guided Machine LearningP41GM103504 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IDEKER, TREY · 2012 to 2024
$17.3M
GenomeSpace: A community web environment for integrative genomic analysisP01HG005062 · NHGRI · BROAD INSTITUTE, INC. · PI MESIROV, JILL P. · 2009 to 2013
$9.1M
Working Memory in Parkinson Disease: A Cognitive & Systems Neuroscience ApproachP50AG047366 · NIA · STANFORD UNIVERSITY · PI HENDERSON, VICTOR · 2015 to 2019
$7.9M
B-Synuclein as a Treatment for Lewy Body DiseaseR01AG018440 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI RISSMAN, ROBERT · 2001 to 2021
$5.2M
NHGRI NIH HHS P01 HG005062NHGRI NIH HHS P01HG005062NIA NIH HHS AG18440/AG/NIANIA NIH HHS AG5131/AG/NIANIA NIH HHS P01 AG019724NIA NIH HHS P01AG019724NIA NIH HHS P01AG16573NIA NIH HHS P50 AG005131NIA NIH HHS P50 AG016573NIA NIH HHS P50 AG016574NIA NIH HHS P50AG016574NIA NIH HHS P50 AG023501NIA NIH HHS P50AG023501NIA NIH HHS P50 AG047366NIA NIH HHS R01 AG018440NIA NIH HHS R01 AG038791NIA NIH HHS R01AG038791NIA NIH HHS R01 AG045034NIA NIH HHS R01AG045034NIA NIH HHS R37 AG018440NIA NIH HHS U01 AG006786NIA NIH HHS U01AG006786NIGMS NIH HHS P41 GM103504NIGMS NIH HHS P41GM103504NIGMS NIH HHS R01 GM084279NIGMS NIH HHS R01GM084279NIMH NIH HHS P30MH06226NIMH NIH HHS P30 MH062261
6 · The paper itself

Abstract

backgroundBiological pathways that significantly contribute to sporadic Alzheimer's disease are largely unknown and cannot be observed directly. Cognitive symptoms appear only decades after the molecular disease onset, further complicating analyses. As a consequence, molecular research is often restricted to late-stage post-mortem studies of brain tissue. However, the disease process is expected to trigger numerous cellular signaling pathways and modulate the local and systemic environment, and resulting changes in secreted signaling molecules carry information about otherwise inaccessible pathological processes.

resultsTo access this information we probed relative levels of close to 600 secreted signaling proteins from patients' blood samples using antibody microarrays and mapped disease-specific molecular networks. Using these networks as seeds we then employed independent genome and transcriptome data sets to corroborate potential pathogenic pathways.

conclusionsWe identified Growth-Differentiation Factor (GDF) signaling as a novel Alzheimer's disease-relevant pathway supported by in vivo and in vitro follow-up experiments, demonstrating the existence of a highly informative link between cellular pathology and changes in circulatory signaling proteins.

Indexed as

ProteomicsAlzheimer DiseaseAmyloid beta-PeptidesAmyloid beta-Protein PrecursorBrainHumansNerve NetSignal TransductionAmyloid beta-PeptidesAmyloid beta-Protein Precursor

Identifiers

PMID27112350
PMCPMC4845325
OpenAlexW2343713183

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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.