Table 2 Summary of techniques of synuclein species quantification in different specimens and findings in PD.

From: Alpha-synuclein in Parkinson’s disease and other synucleinopathies: from overt neurodegeneration back to early synaptic dysfunction

Specimen

Methods

Analyte

Diagnostic meaning

CSF

• ELISA, Electrochemiluminescence, xMAP technology, Single-molecule array technology

t-α-syn

p-α-syn

o-α-syn

↓ in synucleinopathies, ↑ as aspecific marker of synaptic damage

↑ in PD than controls, better diagnostic yield if combined with other α-syn species

↑ in PD than controls, better diagnostic yield if combined with other α -syn species

• Real-Time Quaking-Induced Conversion (RT-QuIC), Protein-Misfolding Cyclic Amplification (PMCA)

misfolded α-syn

Can accurately detect α-syn seeding activity across the spectrum of LB-related disorders

Higher seeding activity of pathologically aggregated α -syn in DLB than PD

• Nanoscale flow cytometry

α-syn–containing extracellular vesicles (EVs)

Total α-syn–positive and aggregated α-syn–positive EV are significantly lower in patients with PD than controls

Blood

• ELISA

t-α-syn

plasma o-α-syn

plasma p-α-syn

Not conclusive results for differentiating controls from diseased groups, possible utility as a marker of disease progression

↑ in PD

↑ in PD

• Nanoscale flow cytometry

α-syn–containing extracellular vesicles (EVs)

↑ in PD

Saliva, tears

• ELISA

t-α-syn

o-α-syn

o-α-syn/t-α-syn

Not statistically significant in distinguishing PD from controls

↑ in PD than controls, correlates with disease duration

↑ in PD than controls, increased in advanced stages

Skin

• Immunohistochemical analysis

t-α-syn

p-α-syn

↑ in PD and synucleinopathies than tauopathies and controls

Skin α-syn deposits differ in clinical variants of synucleinopathy

Retina

• Fluorescence immunohistochemistry

p-α-syn

in the retina of PD patients in parallel with that in the brain, including before clinical onset of the disease.

It correlates with clinical disease severity

Gut mucosa

• Immunohistochemical analysis

t-α-syn

p-α-syn

Conflicting results. More recent studies do not find significant diagnostic value in discriminating PD patients from controls

Gonadal tissue

• Immunohistochemical analysis

p-α-syn

Abundance of p-α-syn in the testicular and ovarian tissue of two PD patients