Table 5.
Results of studies on CSF alpha-synuclein and phosphotau levels in PD, other parkinsonian syndromes and controls.
| References | Cases/Controls | Main findings |
|---|---|---|
| Borghi et al., 2000 | 12 PD, 10 controls | Identification of a 19 kDa band that corresponds to monomeric α-synuclein (similar levels in PD and controls) |
| Woulfe et al., 2002 | 5 PD, 4 controls | Similar anti-α-synuclein antibodies in PD and controls |
| Tokuda et al., 2006 | 33 PD, 38 controls (9 healthy and 29 with OND) | CSF α-synuclein levels significantly lower in PD than in controls (p < 0.0001) |
| Ohrfelt et al., 2009 | 66 AD, 15 PD, 15 DLBD, 55 controls | CSF α-synuclein AD > Controls = DLBD = PD |
| Hong et al., 2010 | 117 PD, 132 controls, 50 AD | CSF α-synuclein PD < Controls = AD (after correcting for hemoglobin levels) |
| Tokuda et al., 2010 | 32 PD, 28 controls (12 healthy and 16 with OND) | CSF α-synuclein oligomers and oligomers/total-α-synuclein ratio in CSF higher in PD group (p < 0.0001) |
| Tokuda et al., 2010 | 25 PD, 18 PSP, 35 AD, 43 controls | CSF α-synuclein PD > PSP = Controls > AD |
| Parnetti et al., 2011 | 38 PD, 32 DLBD, 48 AD, 31 FTD, 32 controls with other neurological diseases (n = 32) | CSF α-synuclein Controls > PD > DLBD = AD = FTD |
| Mollenhauer et al., 2011 | Cross-sectional cohort: 51 PD, 29 MSA, 55 DLBD, 62 AD, and 72 neurological controls | CSF α-synuclein PD < DLBD < MSA < controls < AD |
| Kang et al., 2013 | Validation cohort: 275 PD, 15 MSA, 55 66 DLBD, 8 PSP, 22 NPH, and 23 neurological controls | CSF α-synuclein MSA < DLBD = PD < NPH = PSP < controls |
| Park et al., 2011 | 23 PD, 29 neurological controls | CSF α-synuclein oligomer significantly higher in PD than in neurological controls |
| Kang et al., 2013 | 63 PD, 39 controls | Slightly, but significantly, lower CSF levels of α-synuclein in PD compared with healthy controls |
| Lower levels of CSF α-synuclein associated with increased motor severity | ||
| Hall et al., 2012 | 90 PDND, 33 PDD, 70 DLBD, 48 AD, 45 PSP, 48 MSA, 12 CBD, 107 controls | CSFα-synuclein AD > PSP = Controls > PDD = DLBD = MSA = CBD = PDND |
| Tateno et al., 2012 | 9 AD, 6 DLBD, 11 PD, 11 MSA, 11 neurological controls | CSFα-synuclein levels in AD higher than in controls (P < 0.05), and significantly lower in PD (P < 0.001), DLBD (P < 0.01), and MSA (P < 0.05) when compared with AD |
| Wang et al., 2012 | Discovery series: 93 PD, 26 AD, 78 controls, 33 PSP, 16 MSA | CSF Phosphorylated α-synuclein (PS-129) PD > Controls > AD > MSA = PSP |
| Replication series: 116 PD, 50 AD, 126 controls, 27 PSP, 25 MSA | CSFα-synuclein MSA < PD < PSP > AD = Controls | |
| CSF PS-199/α-synuclein ratio MSA > PK > AD > PSP = Controls | ||
| Aerts et al., 2012 | 58 PD, 47 MSA, 3 DLBD, 22 Vascular Parkinsonsim, 10 PSP, 2 CBD, 57 controls | CSFα-synuclein did not differ significantly among the study groups |
| Foulds et al., 2012 | 13 PDND, 10 PD with cognitive impairment, 16 PDD, 17 DLBD, 12 PSP, 8 MSA, 20 controls (ventricular CSF obtained post-mortem) | CSF total α-synuclein, oligomeric α-synuclein and phosphorylated α-synuclein similar in PDND, PDCI, PDD, DLBD, PSP, MSA, and control groups |
| CSF oligomeric phosphorylated α-synuclein significantly higher in MSA (p < 0.001) when compared with the other study groups | ||
| Shi et al., 2012 | 8 symptomatic and 18 asymptomatic carriers of the G2019 mutation in the LRRK2 gene | Lack of correlation between PET scan evidence of loss of striatal dopaminergic and CSF α-synuclein levels |
| Mollenhauer et al., 2013 | 78 PD (drug naive), 48 controls | CSF α-synuclein lower in PD than in controls |
| Wennström et al., 2013 | 52 controls, 46 AD,38 PDND, 22 PDD, 33 DLBD | AD > controls > DLBD > PD > PDD |
| Parnetti et al., 2014a | 71 PD (8 of 44 carriers of a mutation in the beta-glucocerebrosidase gene (GBA1) 45 controls with other neurological diseases | CSF α-synuclein lower and oligomeric/total α-synuclein ratio higher in PD than in controls |
| Parnetti et al., 2014b | 44 PD and 25 controls with other neurological diseases | CSF total α-synuclein lower and oligomeric α-synuclein higher in PD than in controls. No relation with prognosis and cognitive impairment |
| van Dijk et al., 2014 | 53 PD, 50 controls | CSF α-synuclein levels reduced in patients with PD, but not correlated with measures of disease severity, and striatal dopaminergic deficit assessed with neuroimaging |
| Mondello et al., 2014 | 22 controls, 52 PD, 34 MSA, 32 PSP, 12 CBD | CSF α-synuclein MSA < PD < PSP < CBD < Controls |
| Stewart et al., 2014 | 304 early PD patients enrolled in the DATATOP study. Longitudinal follow-up | CSF α-synuclein showed a longitudinal decrease over follow-up period |
| CSF α-synuclein was not correlated with the rate of clinical progression of the motor symptoms | ||
| Lower basal levels of CSF α-synuclein were associated with better preservation of cognitive function |
AD, Alzheimer's disease; PD, Parkinson's disease; FTD, frontotemporal dementia; PDND, PD non-demented; PD, PD demented; OND, Other neurological diseases; DLBD, diffuse Lewy body disease; PSP, progressive supranuclear palsy; CBD, corticobasal degeneration; MSA, multiple system atrophy; NPH, normal pressure hydrocephalus.