Article

CSF alpha-Synuclein Does Not Discriminate Dementia with Lewy Bodies from Alzheimer's Disease

Department of Neurology and Alzheimer Center, VU University Medical Center, Amsterdam, The Netherlands.
Journal of Alzheimer's disease: JAD (Impact Factor: 4.15). 01/2010; 22(1):87-95. DOI: 10.3233/JAD-2010-100186
Source: PubMed

ABSTRACT In this study, we assessed whether cerebrospinal fluid (CSF) levels of the biomarker α-synuclein have a diagnostic value in differential diagnosis of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). We also analyzed associations between CSF biomarkers and cognitive performance in DLB and in AD. We included 35 DLB patients, 63 AD patients, 18 patients with Parkinson's disease (PD), and 34 patients with subjective complaints (SC). Neuropsychological performance was measured by means of the Mini-Mental Status Examination (MMSE), Visual Association Test (VAT), VAT object-naming, Trail Making Test, and category fluency. In CSF, levels of α-synuclein, amyloid-β 1-42 (Aβ1-42), total tau (tau), and tau phosphorylated at threonine 181 (ptau-181) were measured. CSF α-synuclein levels did not differentiate between diagnostic groups (p=0.16). Higher ptau-181 and higher tau levels differentiated AD from DLB patients (p< 0.05). In DLB patients, lower Aβ1-42 and higher total tau levels were found than in SC and PD patients (p< 0.05). In DLB patients, linear regression analyses of CSF biomarkers showed that lower α-synuclein was related to lower MMSE-scores (β (SE) = 6(2) and p< 0.05) and fluency (β (SE) = 4(2), p< 0.05). Ultimately, CSF α-synuclein was not a useful diagnostic biomarker to differentiate DLB and/or PD (α-synucleinopathies) from AD or SC. In DLB patients maybe lower CSF α-synuclein levels are related to worse cognitive performance.

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    • "Only two studies reported efforts to blind assay results [21] [22] and clinical data [16] while none of the studies attempted to blind the reference standard using an external clinical reviewer. Mean and standard deviation of concentrations of alpha-synuclein between patient subgroups were sometimes not reported as well. "
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    ABSTRACT: Dementia with Lewy Bodies (DLB) can be difficult to distinguish clinically from other dementias. To investigate the diagnostic utility of CSF alpha-synuclein in differentiating between DLB and other dementias. Electronic databases were systematically searched for studies investigating reproducible alpha synuclein quantification methods. Random effects model was used to calculate weighted mean difference (WMD) and 95% confidence intervals between DLB and other groups. A total of 13 studies, comprising 2728 patients were included. Mean CSF alpha-synuclein concentration was significantly lower in DLB patients compared to those with Alzheimers disease (AD) [WMD -0.24; 95% CI, -0.45, -0.03; p = 0.02]. No significant difference was found between patients with DLB compared to Parkinsons disease [WMD 0.05; 95% CI, -0.17, 0.28; p = 0.65] or other neurodegenerative conditions. CSF alpha synuclein may be of diagnostic use in differentiating between DLB and AD. We propose several recommendations to guide better design of future studies.
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    • "However, in a later study (Tokuda et al., 2010) no such clear differences were seen. Elsewhere, Mollenhauer et al. (2008, 2011) have similarly reported a lowering of total α-syn levels between PD patients and controls, though this finding has not been replicated by others (Ohrfelt et al., 2009; Spies et al., 2009; Reesink et al., 2010; Aerts et al., in press). In the present study, using a similar immunoassay protocol to Tokuda et al. (2006, 2010), we also found no significant differences in total α-syn levels between PD patients and controls, or between DLB patients and controls. "
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