Evidence map›Paper›PMID 38467937›Full record

ArticleActa neuropathologica2024

Comprehensive proteomics of CSF, plasma, and urine identify DDC and other biomarkers of early Parkinson's disease.

Jarod Rutledge, Benoit Lehallier, Pardis Zarifkar, Patricia Moran Losada, Marian Shahid-Besanti, Dan Western, Priyanka Gorijala, Sephira Ryman, Maya Yutsis, Gayle K Deutsch and 11 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta neuropathologica, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed, 2 pooled it
29.5field-weighted citation impact, top 1% 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

70 citing papers in PubMed, 2 syntheses or guidelines pooled it, 80 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Cross-tissue immune profiling of APOE ε4 reveals early dysregulation in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

10 more citing papers are in PubMed but not listed here.

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

21 authors at 7 institutions in 3 countries.

Jarod RutledgeDepartment of Genetics, Stanford University School of Medicine, Stanford University, Stanford, CA, USA. jarod@stanford.edu.ORCID 0000-0001-7790-2801
Benoit LehallierDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
Pardis ZarifkarDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
Patricia Moran LosadaDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
Marian Shahid-BesantiDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
Dan WesternDepartment of Psychiatry, Washington University in St Louis, St Louis, MO, USA.
Priyanka GorijalaDepartment of Psychiatry, Washington University in St Louis, St Louis, MO, USA.
Sephira RymanDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
Maya YutsisDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
Gayle K DeutschDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
Elizabeth MorminoDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
Alexandra TrelleDepartment of Psychology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
Anthony D WagnerWu Tsai Neurosciences Institute, Stanford University School of Medicine, Stanford, CA, USA.
Geoffrey A KerchnerDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
Lu TianDepartment of Biomedical Data Science, Stanford University School of Humanities and Sciences, Stanford University, Stanford, CA, USA.
Carlos CruchagaDepartment of Psychiatry, Washington University in St Louis, St Louis, MO, USA.
Victor W HendersonDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
Thomas J MontineDepartment of Pathology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
Per BorghammerDepartment of Nuclear Medicine and PET, Aarhus University Hospital, Aarhus, Denmark.
Tony Wyss-CorayDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford University, Stanford, CA, USA. twc@stanford.edu.
Kathleen L PostonDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford University, Stanford, CA, USA. klposton@stanford.edu.
Stanford University · USNeurosciences Institute · USWashington University in St. Louis · USAarhus University · DKAarhus University Hospital · DKMind Research Network · USRoche (Switzerland) · CH

Funding

Stanford Alzheimer's Disease Research CenterAdmin Supp: Developing iPSC models for AD and PDP30AG066515 · NIA · STANFORD UNIVERSITY · PI Victor Henderson · 2020 to 2026
$29.0M
Working Memory in Parkinson Disease: A Cognitive & Systems Neuroscience ApproachP50AG047366 · NIA · STANFORD UNIVERSITY · PI GREICIUS, MICHAEL D · 2015 to 2019
$7.9M
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
High-resolution imaging of hippocampal mechanisms in age-related memory decline.R01AG048076 · NIA · STANFORD UNIVERSITY · PI WAGNER, ANTHONY D · 2014 to 2018
$1.9M
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 AG066515NIA NIH HHS P50 AG047366NIA NIH HHS R01 AG048076NINDS NIH HHS K23 NS075097NINDS NIH HHS R01 NS115114
6 · The paper itself

Abstract

Parkinson's disease (PD) starts at the molecular and cellular level long before motor symptoms appear, yet there are no early-stage molecular biomarkers for diagnosis, prognosis prediction, or monitoring therapeutic response. This lack of biomarkers greatly impedes patient care and translational research-L-DOPA remains the standard of care more than 50 years after its introduction. Here, we performed a large-scale, multi-tissue, and multi-platform proteomics study to identify new biomarkers for early diagnosis and disease monitoring in PD. We analyzed 4877 cerebrospinal fluid, blood plasma, and urine samples from participants across seven cohorts using three orthogonal proteomics methods: Olink proximity extension assay, SomaScan aptamer precipitation assay, and liquid chromatography-mass spectrometry proteomics. We discovered that hundreds of proteins were upregulated in the CSF, blood, or urine of PD patients, prodromal PD patients with DAT deficit and REM sleep behavior disorder or anosmia, and non-manifesting genetic carriers of LRRK2 and GBA mutations. We nominate multiple novel hits across our analyses as promising markers of early PD, including DOPA decarboxylase (DDC), also known as L-aromatic acid decarboxylase (AADC), sulfatase-modifying factor 1 (SUMF1), dipeptidyl peptidase 2/7 (DPP7), glutamyl aminopeptidase (ENPEP), WAP four-disulfide core domain 2 (WFDC2), and others. DDC, which catalyzes the final step in dopamine synthesis, particularly stands out as a novel hit with a compelling mechanistic link to PD pathogenesis. DDC is consistently upregulated in the CSF and urine of treatment-naïve PD, prodromal PD, and GBA or LRRK2 carrier participants by all three proteomics methods. We show that CSF DDC levels correlate with clinical symptom severity in treatment-naïve PD patients and can be used to accurately diagnose PD and prodromal PD. This suggests that urine and CSF DDC could be a promising diagnostic and prognostic marker with utility in both clinical care and translational research.

Indexed as

Parkinson DiseaseAromatic-L-Amino-Acid DecarboxylasesBiomarkersDopa DecarboxylaseHumansOxidoreductases Acting on Sulfur Group DonorsPlasmaProteomicsAromatic-L-Amino-Acid DecarboxylasesBiomarkersDDC protein, humanDopa DecarboxylaseOxidoreductases Acting on Sulfur Group DonorsSUMF1 protein, human

Identifiers

PMID38467937
PMCPMC10927779
OpenAlexW4392640908

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.