Table 2.

Overview of extracellular vesicle (EV)-associated biomarkers in Parkinson’s disease (PD).

			EV QC				PD vs. ctrl
Source	Cohort	EV Isolation Method	NTA	TEM	EV Markers	Biomarker	Result	Statistics	Reference
CSF	PD: 76 Ctrl: 58	Differential centrifugation	x	x	+; -	α-syn	↓	p < 0.05	[95]
	PD: 9 Ctrl: 9	CD11b immunocapture				α-syn	↑	p < 0.05	[101]
						Oligomeric α-syn
						Fibrillar α-syn	=	ns
Plasma	PD: 267 Ctrl: 215	L1CAM immunocapture		x	+	α-syn Ratio EV α-syn/plasma α-syn	↑	AUC: 0.654	[158]
								AUC: 0.657
	PD: 39 Ctrl: 33	Differential centrifugation	x	x	+; -	α-syn Ratio EV α-syn/plasma α-syn	↑	p < 0.001	[118]
	PD: 20 Ctrl: 15	Differential centrifugation		x	+; -	α-syn	↑	p = 0.02	[103]
						Monomeric and oligomeric α-syn		p = 0.0002; p < 0.0001
						Fibrillar α-syn	=	ns
	PD: 39 Ctrl: 40	ExoQuick + immunoprecipitation with L1CAM		x		α-syn	↑	AUC: 0.654	[159]
						DJ-1		AUC: 0.703
						Ratio EV DJ-1/plasma DJ-1		AUC: 0.724
	PD: 16 Ctrl: 8	Size exclusion chromatography		x	+	Clusterin	↓	p < 0.05	[161]
						Complement C1r
						Apolipoprotein A1
	PD: 52 Ctrl: 48	PureExo exosome isolation kit		x	+	miR-331-5p	↑	AUC: 0.849	[162]
						miR-505	↓	AUC: 0.898
Serum	PD: 14 Ctrl: 14	Differential centrifugation	x	x	+; -	α-syn	↑	p < 0.05	[104]
						Monomeric and oligomeric α-syn		-
						pS129 α-syn
						TNF-α and IL-1β		p < 0.05
	PD: 230 Ctrl: 144	Differential centrifugation + immunoprecipitation with L1CAM	x		+	α-syn	↑	AUC: 0.86	[160]
						Clusterin	=	ns
	PD: 22 Ctrl: 18	Size exclusion chromatography		x	+; -	Raman spectrum	≠	AUC: 0.71	[163]
	PD: 36 Ctrl: 36	Differential centrifugation	x	x	+; -	Protein composition	≠	NA	[156]
	PD: 20 Ctrl: 10	Differential centrifugation				Protein composition	≠	NA	[164]
	PD: 16 Ctrl: 12	Differential centrifugation		x	+; -	ATP5A	↓	p < 0.0001	[157,165]
						NDUFS3
						SDHB
	PD: 109 Ctrl: 40	Total exosome isolation reagent			+	miR-24	↑	AUC: 0.908	[166]
						miR-195		AUC: 0.697
						miR-19b	↓	AUC: 0.753
Urine	PD: 20 Ctrl: 15	Differential centrifugation		x	+	LRKK2	=	ns	[167]
	PD: 26 Ctrl: 21	Microfiltration			+	DJ-1	↑ (only in males)	p = 0.0493	[168]
						LRKK2	=	ns
	LRKK2+ PD: 21 LRKK2- PD: 20 LRKK2+ noPD: 16	Differential centrifugation			+	Ratio pSer1292 LRKK2/total LRKK2	LRKK2+ PD/LRKK2- PD: ↑	AUC: 1	[169]
							LRKK2+ PD/LRKK2+ noPD: ↑	AUC: 0.844
	PD: 79 Ctrl: 79	Differential centrifugation		x	+	pSer1292 LRKK2	↑	p = 0.0014	[170]
	PD: 28 Ctrl: 22	Differential centrifugation	x	x		SNAP23	↑	AUC: 0.8	[171]
						Calbindin		AUC: 0.75
Saliva	PD: 74 Ctrl: 60	XYCQ EV enrichment kit	x	x	+	α-syn	=	ns	[172]
						pS129 α-syn
						Oligomeric α-syn	↑	AUC: 0.941
						Ratio α-syn/oligomeric α-syn		AUC: 0.772
	PD: 18 Ctrl: 5	PEG precipitation	x		+	α-syn	↑	p < 0.0004	[173]
						L1CAM		p < 0.0001

This table only discusses results obtained in Parkinson’s disease (PD) patients and controls (ctrl). In the extracellular vesicle (EV) markers column, the + symbol indicates the assessment of typical EV markers whereas the—symbol indicates the assessment of non-EV markers. For statistics, preferably the area under the receiver operating curve (AUC) or alternatively the sensitivity (sens) and specificity (spec) or p-value are indicated. Abbreviations: QC, quality control; NTA, nanoparticle tracking analysis; TEM, transmission electron microscopy; CSF, cerebrospinal fluid; L1CAM, L1 cell adhesion molecule; α-syn, alpha synuclein; TNF-α, tumor necrosis factor α; IL-1β, interleukin 1 β; NA, not applicable; ATP5A, adenosine triphosphate 5A; NDUFS3, NADH:ubiquinone oxidoreductase subunit S3; SDHB, succinate dehydrogenase complex iron sulfur subunit B; LRKK2, leucine-rich repeat kinase 2; SNAP23, synaptosomal-associated protein 23.