Differential Sialylation of Serpin A1 in the Early Diagnosis of Parkinson's Disease Dementia

被引:28
作者
Jesse, Sarah [1 ]
Lehnert, Stefan [1 ]
Jahn, Olaf [2 ,3 ]
Parnetti, Lucilla [11 ]
Soininen, Hilkka [4 ,5 ]
Herukka, Sanna-Kaisa [4 ,5 ]
Steinacker, Petra [1 ]
Tawfik, Saskia [1 ]
Tumani, Hayrettin [1 ]
von Arnim, Christine A. F. [1 ]
Neumann, Manuela [6 ]
Kretzschmar, Hans A. [7 ]
Kulaksiz, Hasan [8 ]
Lenter, Martin [9 ]
Wiltfang, Jens [10 ]
Ferger, Boris [9 ]
Hengerer, Bastian [9 ]
Otto, Markus [1 ]
机构
[1] Univ Ulm, Dept Neurol, D-7900 Ulm, Germany
[2] Max Planck Inst Expt Med, Prote Grp, D-37075 Gottingen, Germany
[3] DFG Res Ctr Mol Physiol Brain, Gottingen, Germany
[4] Univ Eastern Finland, Dept Neurol, Kuopio, Finland
[5] Kuopio Univ Hosp, SF-70210 Kuopio, Finland
[6] Univ Zurich, Inst Neuropathol, Zurich, Switzerland
[7] Univ Munich, Inst Neuropathol, D-8000 Munich, Germany
[8] Univ Ulm, Dept Internal Med, D-7900 Ulm, Germany
[9] Boehringer Ingelheim GmbH & Co KG, CNS Dis Res, Biberach, Germany
[10] Univ Essen Gesamthsch, Dept Psychiat, Essen, Germany
[11] Univ Perugia, Dept Neurol, I-06100 Perugia, Italy
关键词
ALPHA-SYNUCLEIN; CEREBROSPINAL-FLUID; LEWY BODIES; PROTEIN AGGREGATION; MOLECULAR-BASIS; TASK-FORCE; WORK GROUP; ALZHEIMERS; BRAIN; GLYCOSYLATION;
D O I
10.1371/journal.pone.0048783
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The prevalence of Parkinson's disease (PD) increases with age. Up to 50% of PD show cognitive decline in terms of a mild cognitive impairment already in early stages that predict the development of dementia, which can occur in up to 80% of PD patients over the long term, called Parkinson's disease dementia (PDD). So far, diagnosis of PD/PDD is made according to clinical and neuropsychological examinations while laboratory data is only used for exclusion of other diseases. The aim of this study was the identification of possible biomarkers in cerebrospinal fluid (CSF) of PD, PDD and controls (CON) which predict the development of dementia in PD. For this, a proteomic approach optimized for CSF was performed using 18 clinically well characterized patients in a first step with subsequent validation using 84 patients. Here, we detected differentially sialylated isoforms of Serpin A1 as marker for differentiation of PD versus PDD in CSF. Performing 2D-immunoblots, all PDD patients could be identified correctly (sensitivity 100%). Ten out of 24 PD patients showed Serpin A1 isoforms in a similar pattern like PDD, indicating a specificity of 58% for the test-procedure. In control samples, no additional isoform was detected. On the basis of these results, we conclude that differentially sialylated products of Serpin A1 are an interesting biomarker to indicate the development of a dementia during the course of PD. Citation: Jesse S, Lehnert S, Jahn O, Parnetti L, Soininen H, et al. (2012) Differential Sialylation of Serpin A1 in the Early Diagnosis of Parkinson's Disease Dementia. PLoS ONE 7(11): e48783. doi:10.1371/journal.pone.0048783
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页数:10
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