Table 1.
Fluid and tissue biomarkers of alpha-synuclein pathology.
| Biomarker | Utility for inclusion/exclusion criteria | Utility as an outcome measure | Procedure | Comments |
|---|---|---|---|---|
| CSF, seeded aggregation assay for alpha-synuclein | PD vs. Ctrl: good SN, SP, AUC (0.89–0.95) (6) PD/DLB/PAF: good SN, SP (7) RBD vs. Ctrl: good SN, SP (8) | Changes over time not established. PD: MIF correlates with UPDRS score RBD: PD/DLB risk (8) |
Lumbar puncture | Commercial test to be released in 2021 |
| Skin biopsy, seeded aggregation assay for alpha-synuclein | PD: good SN/SP (9, 10) PD/DLB/MSA vs. other: good SN/SP (10) | Change over time not established PD: MIF correlates with UPDRS and MMSE (9) |
Punch biopsy, frozen | Promising results, numbers of patients still modest, lower SN/SP for FFPE |
| Skin biopsy(-ies), IF synuclein & PGP 9.5 | PD: good SN/SP when optimized (11) PD/DLB/MSA/PAF vs. other: good SN/SP, better for IF vs. CSF or skin RT-QuIC in one study (12) | One study shows 7% increase per year (unpublished) | 1–3 punch biopsies, frozen or ZF | Promising results; needs multisite validation; commercial test offered since 2020 |
| Skin biopsy-single biopsy (scalp), single-label IHC for alpha-synuclein | PD: good SP with optimized methods; SN limited (24%) especially in early PD. Better SN than colon (13) | Changes over time not established | Punch biopsy, FFPE | Not likely to be developed further |
| Submandibular gland biopsy | PD: good SP with optimized methods; limited SN (56%) especially in early PD; better SN than colon and skin (13) | Changes over time not established | Submandibular biopsy by ENT | Not likely to be developed further |
| Colon biopsy | PD: good SP with optimized methods; low SN (<15%) especially in early PD (13) | Changes over time not established | Colonoscopy with biopsy | Not likely to be developed further |
Designation of “good” means >90%. PD, Parkinson's disease; DLBs, dementia with Lewy bodies; PAF, pure autonomic failure; RBD, REM-behavior sleep disorder; UPDRS, Unified Parkinson's Disease Rating Score; MMSE, Mini Mental State Examination; SN, sensitivity; SP, specificity; AUC, area under the curve; MIF, maximum intensity fluorescence; FFPE, formalin-fixed paraffin embedded tissues; IF, immunofluorescence; ZF, Zamboni's fixative.