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. Author manuscript; available in PMC: 2022 May 1.
Published in final edited form as: Lancet Neurol. 2021 May;20(5):385–397. doi: 10.1016/S1474-4422(21)00030-2

Table 4 -.

Candidate biomarkers for Parkinson’s disease

Modality Biomarker Diagnostic Potential Comments
Prodromal PD Manifest PD DD
Non-PD
Progression
MRI Substantia nigra neuromelanin 68,70,71 +? + - + Insufficiently studied in prodromal PD
Dorsolateral nigral hyperintensity74,75 +? + - - Insufficiently studied in prodromal PD
No differentiation PD vs atypical PD
Quantitative Susceptibility Mapping (QSM) 69,72,73 ? + - ? Limited number of studies
Use in DD unclear
No progression data
Tensor Imaging (Free Water MRI; NODDI) 76,77 ? + + ? Role in early/prodromal Dx unclear
No progression data
Automated Volumetry 78,79 - - + + Insufficiently studied in prodromal PD
Mutlimodal MRI80 ? - + ? Insufficiently studied in prodromal PD
No progression data
Radiotracer Imaging A-syn + + +/− + Tracers not yet available
Tau-protein 97 - - + - Mostly studied in AD & PSP/CBD, limited data for PD
Blood Nfl 98 - - + - Non-specific marker for neurodegeneration.
Insufficiently studied in prodromal PD.
CSF a-syn seeding activity
(RTQuiC, PMCA) 8992,94,95
+ + + - May distinguish different a-syn strains in PD vs MSA
Nfl 99 - - + - Non-specific marker for neurodegeneration.
May differentiate PD from Atypical parkinsonism at group level
Insufficiently studied in prodromal PD.
Tissue Biopsies Dermal a-syn 86 (IHC) + + - ? Requires multi-site sampling, limited sensitivity, not specific to PD vs other synucleinopathies
Dermal a-syn seeding activity (RT-QuIC; PMCA) 93 ? + + ? Limited in-vivo information
Olfactory Mucosa a-syn seeding activity (RT-QuIC) 96 +? + ? ? Limited number of studies
GI a-syn 87 ? +/− - ? Invasive, Requires multi-site sampling, limited sensitivity
Salivary gland a-syn 87,88 + + - - Invasive, limited sensitivity
Faeces Gut microbiota ? +/− - - Variable results ref different composition of bacterial microbiome between PD and controls
Digital biomarkers Multiple motor and non-motor assessments / wearable devices100 +? - - + Insufficiently studied in prodromal PD
No differentiation PD vs atypical PD

Abbreviations: DD: differential diagnosis; MRI magnetic resonance imaging; NODDI: neurite orientation dispersion and density imaging; a-syn: alpha-synuclein; Nfl neurofilament; RT-QuIC: Real-time quaking-induced conversion; PMCA: protein misfolding cyclic amplification; IHC: Immunohistochemistry; GI gastrointestinal