Modified serpinA1 as risk marker for Parkinson's disease dementia: Analysis of baseline data

改良的 serpinA1 作为帕金森病痴呆的风险标记:基线数据分析

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作者:Steffen Halbgebauer, Magdalena Nagl, Hans Klafki, Ute Haußmann, Petra Steinacker, Patrick Oeckl, Jan Kassubek, Elmar Pinkhardt, Albert C Ludolph, Hilkka Soininen, Sanna-Kaisa Herukka, Jens Wiltfang, Markus Otto

Abstract

Early detection of dementia in Parkinson disease is a prerequisite for preventive therapeutic approaches. Modified serpinA1 in cerebrospinal fluid (CSF) was suggested as an early biomarker for differentiation between Parkinson patients with (PDD) or without dementia (PD). Within this study we aimed to further explore the diagnostic value of serpinA1. We applied a newly developed nanoscale method for the detection of serpinA1 based on automated capillary isoelectric focusing (CIEF). A clinical sample of 102 subjects including neurologically healthy controls (CON), PD and PDD patients was investigated. Seven serpinA1 isoforms of different charge were detected in CSF from all three diagnostic groups. The mean CSF signals of the most acidic serpinA1 isoform differed significantly (p < 0.01) between PDD (n = 29) and PD (n = 37) or CON (n = 36). Patients above the cut-off of 6.4 have a more than six times higher risk for an association with dementia compared to patients below the cut off. We propose this serpinA1 CIEF-immunoassay as a novel tool in predicting cognitive impairment in PD patients and therefore for patient stratification in therapeutic trials.

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