Quantification of CSF and Blood Alpha-Synuclein As a Diagnostic Marker for Synucleinopathies
Alzheimer's & Dementia(2009)
Abstract
Evaluate weather the quantification of α-synuclein (aSyn) in cerebrospinal fluid (CSF) and/or peripheral blood can help to diagnose aSyn-related disorders intra vitam. We hypothesized that aSyn values are decreased in CSF and are elevated in blood in subjects with Parkinson disease (PD) and other synucleinopathies when compared to age-matched healthy (HCO) and neurological controls (NCO). ASyn is an abundantly expressed, neuronal and hematological protein that's linked to the development of PD, dementia with Lewy Bodies (DLB) and Multiple system atrophy (MSA) by genetics and neuropathology. After studying the constitutive release of aSyn by dopamine cells, the unexpected presence of aSyn in choroid plexus epithelium, which produces >75% of CSF and the ultimate identification of aSyn from cell-free CSF after purification by mass spectrometry, we developed a highly sensitive and aSyn-specific enzyme-linked immunoadsorbent assay (ELISA) for the direct quantification of lower picomolar amounts of aSyn using 96- and 384-well plates loading 200 or 50 μl unconcentrated CSF (Mollenhauer et al., 2008). We first carried out cross-sectional studies of 273 patients who were diagnosed with advanced PD, DLB, MSA and in NCO subjects with e.g. Alzheimer disease (AD). In 41 cases the diagnosis was confirmed by autopsy [DLB (n = 13), AD (n = 21) and NCO (n = 7); total n = 41]. For evaluation of the aSyn levels in peripheral blood we also carried out a longitudinal, case-control cohort (n = 319) including HCO (n = 85). We recorded the lowest CSF aSyn concentrations in clinically suspected synucleinopathy cases (PD, DLB and MSA); when compared with AD subjects and with NCO cases (p < 0.05). This reduction in CSF was also observed in independent, smaller cohort, where importantly, the working diagnosis was confirmed at autopsy (DLB versus AD and NCO; p < 0.05). Results on plasma aSyn revealed a statistically significant reduction in PD donors when compared with HCO (p < 0.04) and NCO (p < 0.02) subjects by ANOVA. ANCOVA testing to covary the total protein content of plasma confirmed the significant reduction of aSyn in PD vs NCO patients (p < 0.02; PD vs HCO, p < 0.06). We conclude that laboratory testing based on CSF and plasma may help to assess the diagnosis of synucleinopathies.
MoreTranslated text
Key words
a-Synuclein
AI Read Science
Must-Reading Tree
Example
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
Generate MRT to find the research sequence of this paper
Chat Paper
Summary is being generated by the instructions you defined