Evidence map›Paper›PMID 39342078›Full record

ArticleClinical proteomics2024

Biomarker discovery in progressive supranuclear palsy from human cerebrospinal fluid.

Yura Jang, Sungtaek Oh, Anna J Hall, Zhen Zhang, Thomas F Tropea, Alice Chen-Plotkin, Liana S Rosenthal, Ted M Dawson, Chan Hyun Na, Alexander Y Pantelyat

Abstract read
In one paragraph

Article in Clinical proteomics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Animals : an open access journal from MDPI · 2026
    Article
  2. Review
  3. Review
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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

10 authors.

Yura Jang *Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Sungtaek Oh *Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Anna J HallDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Zhen ZhangDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Thomas F TropeaDepartment of Neurology, Perelman School of Medicine, Philadelphia, PA, USA.
Alice Chen-PlotkinDepartment of Neurology, Perelman School of Medicine, Philadelphia, PA, USA.
Liana S RosenthalDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Ted M DawsonNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA. tdawson@jhmi.edu.
Chan Hyun NaNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA. chanhyun@jhmi.edu.
Alexander Y PantelyatDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. apantel1@jhmi.edu.

Funding

Research Education ComponentP30AG066507 · NIA · JOHNS HOPKINS UNIVERSITY · PI JUAN TRONCOSO · 2020 to 2026
$29.3M
Research Education ComponentP30AG072979 · NIA · UNIVERSITY OF PENNSYLVANIA · PI DAVID A WOLK · 2021 to 2026
$24.8M
Project IV: In Vivo Dissection of Genetic Modifiers on Different Stages of SynucleinopathyP01AG084497 · NIA · UNIVERSITY OF PENNSYLVANIA · PI ALICE S CHEN-PLOTKIN · 2024 to 2026
$15.2M
BIOMARKER DISCOVERY AND VALIDATION IN PSPU01NS102035 · NINDS · JOHNS HOPKINS UNIVERSITY · PI PANTELYAT, ALEXANDER Y. · 2018 to 2022
$4.5M
Biomarkers of cognitive decline in Parkinson's DiseaseR01NS115139 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI CHEN-PLOTKIN, ALICE S · 2019 to 2023
$3.6M
Understanding biomarkers of cognitive decline in Lewy body diseasesR37NS115139 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI ALICE S CHEN-PLOTKIN · 2024 to 2026
$2.2M
Fourier Transform Orbitrap Fusion Lumos Tribrid Mass Spectrometer with ETDS10OD021844 · OD · JOHNS HOPKINS UNIVERSITY · PI PANDEY, AKHILESH · 2016 to 2016
$1.1M
NIA NIH HHS P01 AG084497NIA NIH HHS P30 AG066507NIA NIH HHS P30 AG072979NIH HHS S10 OD021844NINDS NIH HHS R01 NS115139NINDS NIH HHS R37 NS115139NINDS NIH HHS U01 NS102035NINDS NIH HHS U01NS102035
6 · The paper itself

Abstract

backgroundProgressive supranuclear palsy (PSP) is a neurodegenerative disorder often misdiagnosed as Parkinson's Disease (PD) due to shared symptoms. PSP is characterized by the accumulation of tau protein in specific brain regions, leading to loss of balance, gaze impairment, and dementia. Diagnosing PSP is challenging, and there is a significant demand for reliable biomarkers. Existing biomarkers, including tau protein and neurofilament light chain (NfL) levels in cerebrospinal fluid (CSF), show inconsistencies in distinguishing PSP from other neurodegenerative disorders. Therefore, the development of new biomarkers for PSP is imperative.

methodsWe conducted an extensive proteome analysis of CSF samples from 40 PSP patients, 40 PD patients, and 40 healthy controls (HC) using tandem mass tag-based quantification. Mass spectrometry analysis of 120 CSF samples was performed across 13 batches of 11-plex TMT experiments, with data normalization to reduce batch effects. Pathway, interactome, cell-type-specific enrichment, and bootstrap receiver operating characteristic analyses were performed to identify key candidate biomarkers.

resultsWe identified a total of 3,653 unique proteins. Our analysis revealed 190, 152, and 247 differentially expressed proteins in comparisons of PSP vs. HC, PSP vs. PD, and PSP vs. both PD and HC, respectively. Gene set enrichment and interactome analysis of the differentially expressed proteins in PSP CSF showed their involvement in cell adhesion, cholesterol metabolism, and glycan biosynthesis. Cell-type enrichment analysis indicated a predominance of neuronally-derived proteins among the differentially expressed proteins. The potential biomarker classification performance demonstrated that ATP6AP2 (reduced in PSP) had the highest AUC (0.922), followed by NEFM, EFEMP2, LAMP2, CHST12, FAT2, B4GALT1, LCAT, CBLN3, FSTL5, ATP6AP1, and GGH.

conclusionBiomarker candidate proteins ATP6AP2, NEFM, and CHI3L1 were identified as key differentiators of PSP from the other groups. This study represents the first large-scale use of mass spectrometry-based proteome analysis to identify cerebrospinal fluid (CSF) biomarkers specific to progressive supranuclear palsy (PSP) that can differentiate it from Parkinson's disease (PD) and healthy controls. Our findings lay a crucial foundation for the development and validation of reliable biomarkers, which will enhance diagnostic accuracy and facilitate early detection of PSP.

Indexed as

BiomarkersCerebrospinal fluidMass spectrometryProgressive supranuclear palsyProteomics

Identifiers

PMID39342078
PMCPMC11437921

What Socratic holds

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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 Socratic graph.