𝜶-Synuclein as CSF and Blood Biomarker of Dementia with Lewy Bodies

Table 1

Studies on quantification of α-synuclein level in CSF of patients with DLB and other synucleinopathies.

Level of total α-synuclein	Study	Blood contamination; was considered*	Controls			Synucleinopathies
			Healthy controls	Neurological controls	AD	Lewy body diseases			Results
						DLB	PD	MSA
	Tokuda et al. [31]	No	9	29	—	—	33	—	PD patients showed significantly lower α-syn level than the controls (𝑃<0.0001). The level of α-syn decreased significantly with age (𝑃=0.0076) and correlated to inversely assigned Hoehn and Yahr stage (𝑃<0.0001).
	Mollenhauer et al. [28]	No	—	13	13	38	8	—	The level of α-syn in DLB and PD patients were lower than AD patients and controls (𝑃=0.025).
	Kasuga et al. [32]	No	—	21	31	34	—	—	The level of α-syn in DLB patients was significantly lower than those in patients with AD (𝑃<0.05) and other dementias (𝑃<0.01). In DLB patients, reduced α-syn level correlated with the lower level of CSF Aβ42 (𝑃=0.01). Patients with SNCA duplication showed a decrease of CSF α-syn.
	Tokuda et al. [44]	No	16	12	—	—	32	—	The level of total α-syn was lower in PD patients than in age-matched controls. The level of α-syn oligomers was significantly higher in PD patients than in age-matched controls.
	Mollenhauer et al. [34]	Yes	—; —	76; 20	62; 3	55; 66	51; 273	29; 15	Upper and lower rows indicate training and validation cohorts, respectively. The level of α-syn was significantly lower in DLB, PD, and MSA patients than in other neurological diseases.
	Hong et al. [33]	Yes	92	—	38	—	86	20	The level of α-syn was decreased in PD and MSA patients.
	Parnetti et al. [37]	Yes	—	32	48	32	38	—	The level of α-syn was lower in patients with neurodegenerative diseases than in cognitively normal subjects, but the level of α-syn alone did not distinguish synucleinopathies from tauopathies. An inverse correlation between α-syn and total tau levels was observed (𝑃<0.01).
	Tateno et al. [36]	No	—	11	9	6	11	11	The levels of α-syn of DLB, PD, and MSA were lower than AD.
	Wennstrom et al. [38]	No	24	—	26	18	—	—	The level of α-syn in female DLB patients was lower than AD (𝑃=0.041) patients and controls (𝑃=0.028).
	Öhrfeltet al. [45]	Yes	55	—	66	15	15	—	PD, DLB patients and controls showed comparable levels of α-syn. AD patients showed significantly lower level of α-syn than the controls (𝑃<0.001). AD patients with MMSE scores below 20 had significantly lower level of α-syn than AD patients with MMSE scores of 20 or higher (𝑃=0.02).
	Noguchi-Shinohara et al. [46]	No	—	—	21	16	—	—	The level of α-syn did not differ between DLB and AD patients. In DLB patients, the duration of illness was associated with lower level of α-syn (𝑃<0.05).
	Spies et al. [47]	No	57	—	131	40	—	—	The level of α-syn was comparable between DLB, AD, and controls. The level of α-syn decreased with age (𝑃=0.001).
	Reesink et al. [48]	Yes	34	—	63	35	18	—	The level of α-syn was not different among PD, DLB, AD, and controls. In DLB patients, lower α-syn was related to lower MMSE scores (𝑃<0.05) and worse category fluency (𝑃<0.05).
	Aerts et al. [49]	Yes	57	—	—	3	58	47	The level of α-syn was comparable among PD, MSA, DLB patients and controls. In PD group, the level of α-syn was negatively correlated with age at time of lumber puncture (𝑃<0.006).
	Foulds et al. [50]	Yes	20	—	—	16	38	8	The level of total α-syn was not different between PD, DLB, MSA and control groups. Oligomeric phosphorylated α-syn was significantly high in patients with MSA (𝑃<0.001).
	Park et al. [51]	No	18	11	—	—	23	—	The level of total α-syn in PD patients was comparable to that of control groups. The level of α-syn oligomer in PD patients was significantly higher than controls (𝑃=0.005).

Arrows indicate decreased (↓) and comparable (→) levels α-synuclein. Sample numbers are shown in each category. *Erythrocyte counts or haemoglobin levels were considered as a confounding factor. AD: Alzheimer’s disease; DLB: dementia with Lewy bodies; PD: Parkinson’s disease; MSA: multiple system atrophy; α-syn: α-synuclein; MMSE: minimental state examination.