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

التفاصيل البيبلوغرافية
العنوان:	Comprehensive proteomics of CSF, plasma, and urine identify DDC and other biomarkers of early Parkinson's disease.
المؤلفون:	Rutledge J; Department of Genetics, Stanford University School of Medicine, Stanford University, Stanford, CA, USA. jarod@stanford.edu.; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford University, Stanford, CA, USA. jarod@stanford.edu., Lehallier B; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford University, Stanford, CA, USA., Zarifkar P; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.; Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark., Losada PM; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.; Wu Tsai Neurosciences Institute, Stanford University School of Medicine, Stanford, CA, USA., Shahid-Besanti M; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford University, Stanford, CA, USA., Western D; Department of Psychiatry, Washington University in St Louis, St Louis, MO, USA.; NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO, USA., Gorijala P; Department of Psychiatry, Washington University in St Louis, St Louis, MO, USA.; NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO, USA., Ryman S; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.; Translational Neuroscience, Mind Research Network, Albuquerque, NM, USA., Yutsis M; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford University, Stanford, CA, USA., Deutsch GK; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford University, Stanford, CA, USA., Mormino E; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford University, Stanford, CA, USA., Trelle A; Department of Psychology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA., Wagner AD; Wu Tsai Neurosciences Institute, Stanford University School of Medicine, Stanford, CA, USA.; Department of Psychology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA., Kerchner GA; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.; Roche Medical, Basel, Switzerland., Tian L; Department of Biomedical Data Science, Stanford University School of Humanities and Sciences, Stanford University, Stanford, CA, USA., Cruchaga C; Department of Psychiatry, Washington University in St Louis, St Louis, MO, USA.; NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO, USA., Henderson VW; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.; Department of Epidemiology and Population Health, Stanford University, Stanford, CA, USA., Montine TJ; Department of Pathology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA., Borghammer P; Department of Nuclear Medicine and PET, Aarhus University Hospital, Aarhus, Denmark., Wyss-Coray T; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford University, Stanford, CA, USA. twc@stanford.edu.; Wu Tsai Neurosciences Institute, Stanford University School of Medicine, Stanford, CA, USA. twc@stanford.edu.; The Knight Initiative for Brain Resilience, Stanford University, Stanford, CA, USA. twc@stanford.edu., Poston KL; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford University, Stanford, CA, USA. klposton@stanford.edu.; Wu Tsai Neurosciences Institute, Stanford University School of Medicine, Stanford, CA, USA. klposton@stanford.edu.; The Knight Initiative for Brain Resilience, Stanford University, Stanford, CA, USA. klposton@stanford.edu.; Department of Neurosurgery, Stanford University School of Medicine, Stanford University, Stanford, CA, USA. klposton@stanford.edu.
المصدر:	Acta neuropathologica [Acta Neuropathol] 2024 Mar 11; Vol. 147 (1), pp. 52. Date of Electronic Publication: 2024 Mar 11.
نوع المنشور:	Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة:	English
بيانات الدورية:	Publisher: Springer Verlag Country of Publication: Germany NLM ID: 0412041 Publication Model: Electronic Cited Medium: Internet ISSN: 1432-0533 (Electronic) Linking ISSN: 00016322 NLM ISO Abbreviation: Acta Neuropathol Subsets: MEDLINE
أسماء مطبوعة:	Original Publication: Berlin : Springer Verlag
مواضيع طبية MeSH:	Parkinson Disease/diagnosis , Parkinson Disease/genetics, Humans ; Dopa Decarboxylase/genetics ; Proteomics ; Biomarkers/cerebrospinal fluid ; Plasma/metabolism ; Oxidoreductases Acting on Sulfur Group Donors ; Aromatic-L-Amino-Acid Decarboxylases
مستخلص:	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. (© 2024. The Author(s).)
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معلومات مُعتمدة:	K23 NS075097 United States NS NINDS NIH HHS; R01 NS115114 United States NS NINDS NIH HHS; R01 AG048076 United States AG NIA NIH HHS; P50 AG047366 United States AG NIA NIH HHS; P30 AG066515 United States AG NIA NIH HHS
المشرفين على المادة:	EC 4.1.1.- (Dopa Decarboxylase) 0 (Biomarkers) EC 3.1.6.- (SUMF1 protein, human) EC 1.8.- (Oxidoreductases Acting on Sulfur Group Donors) EC 4.1.1.28 (DDC protein, human) EC 4.1.1.28 (Aromatic-L-Amino-Acid Decarboxylases)
تواريخ الأحداث:	Date Created: 20240312 Date Completed: 20240313 Latest Revision: 20240621
رمز التحديث:	20240622
مُعرف محوري في PubMed:	PMC10927779
DOI:	10.1007/s00401-024-02706-0
PMID:	38467937
قاعدة البيانات:	MEDLINE

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تدمد:	1432-0533
DOI:	10.1007/s00401-024-02706-0