کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6019458 | 1186561 | 2008 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Direct quantification of CSF α-synuclein by ELISA and first cross-sectional study in patients with neurodegeneration
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
عصب شناسی
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چکیده انگلیسی
Because accumulation of α-synuclein (αS) in the brain is a hallmark of Parkinson disease (PD) and related disorders, we examined its occurrence in human cerebrospinal fluid (CSF). Following affinity enrichment and trypsin digestion of CSF collected from a neurologically healthy donor, we identified several αS-derived peptides by mass spectrometry. The concentration of αS amounted to < 0.001% of the CSF proteome. We then built, validated and optimized a sandwich-type, enzyme-linked immunoadsorbent assay (ELISA) to measure total αS levels in unconcentrated CSF. In a cross-sectional study of 100 living donors, we examined cell-free CSF samples from subjects clinically diagnosed with advanced PD, dementia with Lewy bodies (DLB), Alzheimer disease (AD), and a group of non-neurodegenerative disease controls (NCO). In these four groups the CSF αS concentrations ranged from 0.8 to 16.2 pg/μl. Mean CSF αS values were lower in donors with a primary synucleinopathy (PD, DLB: n = 57) than in the other two groups (AD, NCO: n = 35; p = 0.025). By contrast, living Creutzfeldt-Jakob disease patients showed markedly elevated CSF αS levels (n = 8; mean, 300 pg/μl; p < 0.001). Our results unequivocally confirm the presence of αS in adult human CSF. In a first feasibility study employing a novel ELISA, we found relatively low CSF αS concentrations in subjects with parkinsonism linked to synucleinopathy, PD and DLB. In definite prion disease cases, we recorded a marked rise in total CSF αS resulting from rapid cell death. Our results will likely aid future biomarker explorations in neurodegenerative conditions and facilitate target validation studies.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Neurology - Volume 213, Issue 2, October 2008, Pages 315-325
Journal: Experimental Neurology - Volume 213, Issue 2, October 2008, Pages 315-325
نویسندگان
Brit Mollenhauer, Valerie Cullen, Ilana Kahn, Bryan Krastins, Tiago F. Outeiro, Imelda Pepivani, Juliana Ng, Walter Schulz-Schaeffer, Hans A. Kretzschmar, Pamela J. McLean, Claudia Trenkwalder, David A. Sarracino, Jean-Paul VonSattel, Joseph J. Locascio,