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Cerebrospinal fluid alpha-synuclein in neurodegenerative disorders - a marker of synapse loss? Neurosci Lett

Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
Neuroscience Letters (Impact Factor: 2.06). 12/2008; 450(3):332-5. DOI: 10.1016/j.neulet.2008.11.015
Source: PubMed

ABSTRACT The association of alpha-synuclein (alpha-syn) neuropathology with Parkinson's disease (PD) and several related disorders has led to an intense research effort to develop cerebrospinal fluid (CSF)- or blood-based alpha-syn biomarkers for these types of diseases. Recent studies show that alpha-syn is present in CSF and possible to measure using enzyme-linked immunosorbent assay (ELISA). Here, we describe a novel ELISA that allows for quantification of alpha-syn in CSF down to 50pg/mL. The diagnostic value of the test was assessed using CSF samples from 66 Alzheimer's disease (AD) patients, 15PD patients, 15 patients with dementia with Lewy bodies (DLB) and 55 cognitively normal controls. PD and DLB patients and controls displayed similar CSF alpha-syn levels. AD patients had significantly lower alpha-syn levels than controls (median [inter-quartile range] 296 [234-372] and 395 [298-452], respectively, p<0.001). Moreover, AD patients with mini-mental state examination (MMSE) scores below 20 had significantly lower alpha-syn than AD patients with MMSE scores of 20 or higher (p=0.02). There was also a tendency towards a negative correlation between alpha-syn levels and disease duration in the AD group (r=-0.247, p=0.06). Altogether, our results speak against CSF alpha-syn as a reliable biomarker for PD and DLB. The lower alpha-syn levels in AD, as well as the association of alpha-syn reduction with AD severity, approximated by MMSE, suggests that it may be a general marker of synapse loss, a hypothesis that warrants further investigation.

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    • "The degree of change of CSF aSyn in Parkinson's disease is only minor, with aSyn being in the range of 80%e90% of the level in matched controls. Discrepant findings showing no change or elevated levels have been reported by other groups (Aerts et al., 2012; Lee et al., 2011; Noguchi-Shinohara et al., 2009; Ohrfelt et al., 2009; Park et al., 2011; Reesink et al., 2010; Spies et al., 2009; Wang et al., 2012). Several factors could explain these discrepancies , including the use of different assay formats and antibodies as well as differences in sample handling (Mollenhauer et al., 2010). "
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    • "This observation was most marked (p < 0.05) in a subgroup of patients with PDD carrying the apolipoprotein genotype epsilon3/epsilon3 Parnetti et al., 2008 19 DLBD, 18 PDD, 23 AD, 20 PDND, 20 controls DLBD showed the lowest mean CSF Aβ42 levels, with a negative association to dementia duration. PDD patients had mean CSF Aβ42 similar to those seen in PD patients Ohrfelt et al., 2009 66 AD patients, 15 PD patients, 15 patients with dementia with Lewy bodies (DLBD) and 55 cognitively normal controls CSF Aβ42 AD < DLBD < PD = Controls Compta et al., 2009b 20 PDND, 20 PDD, 30 controls patients CSF Aβ42 ranged from high (controls) to intermediate (PDND) and low (PDD) levels (P < 0.001). In all PD and PDD patients, in PDND, CSF Aβ42 was related with phonetic fluency Alves et al., 2010 109 PDND, 36 controls, 20 mild AD CSF Aβ42 (19%; p = 0.009), Aβ40 (15.5%; p = 0.008), and Aβ38 (23%; p = 0.004) significantly decreased in PD compared with controls CSF Aβ42 reductions in PD less marked than in AD (53%; p = 0.002) "
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    • "In addition to muscle activity patterns, investigators have studied the utility of putative biomarkers and their prognostic features and association with PD progression. Indeed, some PD-related biomarker candidates have been prospectively proven in clinical biomarker research, of which plasma α-synuclein was found to be a comparatively ideal biomarker and valuable in the diagnosis or monitoring of PD disease progression [13]–[16]. Our collaborator's study implied a trend of decreased plasma α-synuclein and DJ-1 levels in PD patients compared with healthy controls, but no statistical difference was reached [17]. "
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