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Biomarkers discovery for progressive supranuclear palsy from the human cerebrospinal fluid using mass spectrometry-based proteomics

ABSTRACT: Progressive supranuclear palsy (PSP) is a neurodegenerative parkinsonian disorder. This study using CSF samples of PSP patients is a follow-up study to discover biomarkers related to the previous PSP brain results. This study is the first-ever attempt at an in-depth global proteomic study using more than 100 CSF samples for PSP study. In this study, we used the 11-plex isobaric tandem-mass-tag (TMT) technology for more accurate and sensitive quantification of CSF proteins and analyzed them using Orbitrap Fusion Lumos mass spectrometry on 40 PSP and 40 PD patients as well as 40 HC individuals CSF samples for the discovery experiment. These candidate biomarkers discovered in this study will pave the way for the development of reliable PSP biomarkers.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cerebrospinal Fluid

SUBMITTER: chanhyun na

LAB HEAD: Chan-Hyun Na

PROVIDER: PXD041417 | Pride | 2025-05-06

REPOSITORIES: Pride

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Biomarker discovery in progressive supranuclear palsy from human cerebrospinal fluid.

Jang Yura Y Oh Sungtaek S Hall Anna J AJ Zhang Zhen Z Tropea Thomas F TF Chen-Plotkin Alice A Rosenthal Liana S LS Dawson Ted M TM Na Chan Hyun CH Pantelyat Alexander Y AY

Clinical proteomics 20240928 1

<h4>Background</h4>Progressive 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 ...[more]

PMID: 39342078

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Project description:Progressive supranuclear palsy (PSP) is a neurodegenerative disorder clinically characterized by progressive postural instability, supranuclear gaze palsy, parkinsonism, and cognitive decline caused by degeneration in specific areas of the brain including globus pallidus (GP), substantia nigra, and subthalamic nucleus. However, the pathogenetic mechanism of PSP remains unclear to date. Unbiased global proteome analysis of patients’ brain samples is an important step toward understanding PSP pathogenesis, as proteins serve as workhorses and building blocks of the cell. In this study, we conducted unbiased mass spectrometry-based global proteome analysis of GP samples from 15 PSP patients, 15 Parkinson disease (PD) patients, and 15 healthy control (HC) individuals. To analyze 45 samples, we conducted 5 batches of 11-plex isobaric tandem mass tag (TMT)-based multiplexing experiments, identifying 10,231 proteins. The gene set enrichment analysis results showed that the PD pathway was the most highly enriched, followed by pathways for oxidative phosphorylation, Alzheimer disease, Huntington disease, and non-alcoholic fatty liver disease (NAFLD) when PSP was compared to HC or PD. Most of the proteins enriched in the gene set enrichment analysis were mitochondrial proteins such as cytochrome c oxidase, NADH dehydrogenase, acyl carrier protein, succinate dehydrogenase, ADP/ATP translocase, cytochrome b-c1 complex, and/or ATP synthase. Strikingly, all of the enriched mitochondrial proteins in the PD pathway were downregulated in PSP compared to both HC and PD. The subsequent Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) protein-protein interaction (PPI) analysis and the weighted gene co-expression network analysis (WGCNA) further supported that the mitochondrial proteins were the most highly enriched in PSP. This is the first global proteome analysis of human GP from PSP patients, and this study paves the way to understanding the pathogenesis mechanism of PSP.

			Action	DRS
	PSP_CSF_Set10_F01.raw	Raw
	PSP_CSF_Set10_F02.raw	Raw
	PSP_CSF_Set10_F03.raw	Raw
	PSP_CSF_Set10_F04.raw	Raw
	PSP_CSF_Set10_F05.raw	Raw