Table 2.

Selected studies of plasma alpha-synuclein in PD

Study	Biomarker	Subjects	PD duration	Assay specifics	Group comparisons	Clinical correlates
Chen et al. [95]	t-aSyn, Abeta42, Abeta40, t-tau	60 PD 28 HC	median 1y (IQR 0–3)	Immunomagnetic reduction-based immunoassay (MF-ASC-0060)	t-aSyn ↑PD v HC	↑plasma aSyn correlated with: ↑UPDRS, ↑HY, ↓MMSE ↑plasma t-tau correlated with: ↑UPDRS, ↑HY, ↓MMSE ↑plasma Abeta40 correlated with: ↓UPDRS, ↓HY, ↑MMSE
Ng et al. [13]	t-aSyn	170 PD 51 HC	5.0y ± 5.0	SIMOA (Quanterix) Antibodies not disclosed	t-aSyn ↑PD v HC	No change in HY. PD with UPDRS III > 24 or with MMSE ≤ 25 had higher t-aSyn than controls
Chang et al. [96]	t-aSyn serum aSyn	88 PD 40 HC	9.1y ± 6.5	Immunomagnetic reduction assay aSyn 121–125	Plasma and serum t-aSyn ↑PD v HC AUC 0.99, .92	Serum aSyn correlated with HY 1–3 but not plasma aSyn
Youssef et al. [62]	t-aSyn	49 PD 47 HC	4y ± 0.3	ELISA aSyn 118–122/ aSyn 103–108 (Biolegend) ELISA aSyn 110–125/ unmapped detection aSyn Ab (15–125) (Mesoscale Discovery) SIMOA ADx301/ ADx302 (Quanterix)	t-aSyn ↑PD v HC for all assays albeit at different degrees SIMOA assay detecting 8–10 × more plasma aSyn than other assays in both HC and PD cases R = 0.62–0.67 p < 0.0001 for correlations between assays	No correlations with age at diagnosis, disease duration, HY score
Foulds et al. [106]	t-aSyn and p-aSyn	189 PD 91 HC	5.1y ± 4.1	ELISA t-aSyn aSyn 211/ aSyn FL-40 p-aSyn aSyn N19/ aSyn pSer129	t-aSyn: trend towards ↑PD v HC (p = 0.058) at baseline t-aSyn increases over time p-aSyn ↑PD v HC at baseline no change over time
Duran et al. [98]	t-aSyn	53 PD untreated 42 PD treated 60 HC	PD untreated: 0y PD treated: 9.2 ± 1.1	ELISA Invitrogen KHB0061	t-aSyn ↑ PD v HC t-aSyn = PD untreated v PD treated
Lee et al. [99]	t-aSyn	105 PD 38 MSA 51 HC	PD 3.7y ± 3 MSA 3.9y ± 2.3	ELISA aSyn 117–131/ ‘rabbit aSyn antibody’	t-aSyn ↑ PD v HC t-aSyn ↑ MSA v HC Plasma aSyn ↑ PD v MSA	No correlations with age or HY
Gorostidi et al. [104]	t-aSyn, o-aSyn	134 PD 32 PD LRRK2 109 HC	PD 6.2 ± 5.3 PD LRRK2 7.5 ± 6.3	ELISA t-aSyn aSyn 211/ aSyn FL-140 ELISA o-aSyn aSyn 211/ aSyn 211	t-aSyn ↓ in PD v HC t-aSyn = in PD LRRK2 v HC	No correlations with age, disease duration, HY
Li et al. [14]	t- aSyn	13 EO PD 14 LO PD 11 HC	> 5y	Quantitative WB aSyn 97/8	t-aSyn ↓ EO and LO PD v HC
Caranci et al. [102]	t-aSyn	69 PD 110 HC	10.8y ± 7.3	ELISA Invitrogen KHB0061	No difference in t-aSyn between PD and HC or PD men v women	↓ t-aSyn associated with worse HY, UPDRS scores, and cognitive status in men only
Fan et al. [100]	t-aSyn NLRP3	43 PD 24 HC	2.3y ± 0.3	UPlex Assay (Mesoscale Discovery) No information on antibodies	t-aSyn ↑PD v HC t-aSyn correlates with IL-1β	↑ t-aSyn associated with worse UPDRSIII scores
Lin et al. [101]	t-aSyn	80 PD 34 HC	7.5y ± 5.2	Immunomagnetic reduction aSyn211/ aSyn1-140	t-aSyn ↑PD v HC	↑ t-aSyn PDD > PD with normal cognition and with higher HY stage
Shim et al. [103]	t-aSyn	20 PD 20 HC	Not reported	ELISA 4B12/ 4D6	t-aSyn PD = HC t-aSyn correlates with hemolysis	No correlation of aSyn with HY or age

t-aSyn total alpha-synuclein, o-aSyn oligomeric alpha-synuclein, p-aSyn phosphorylated alpha-synuclein, t-tau total tau, p-tau phosphorylated tau, HC healthy controls, OND other neurological disease, AUC area under curve, HY Hoehn and Yahr scale, UPDRS Unified Parkinson’s disease rating scale, MMSE minimental status exam, ELISA enzyme linked immunosorbent assay, SIMOA single molecule array, EO PD early onset PD, LO PD late onset PD, LRRK2 leucine rich repeat kinase 2, PDD parkinson’s disease dementia