Biomarkers of Parkinson's disease in perspective of early diagnosis and translation of neurotrophic therapies

Abstract Parkinson's disease (PD) is a common neurodegenerative disorder characterized by progressive loss of dopamine neurons and aberrant deposits of alpha‐synuclein (α‐syn) in the brain. The symptomatic treatment is started after the onset of motor manifestations in a late stage of the disease. Preclinical studies with neurotrophic factors (NTFs) show promising results of disease‐modifying neuroprotective or even neurorestorative effects. Four NTFs have entered phase I–II clinical trials with inconclusive outcomes. This is not surprising because the preclinical evidence is from acute early‐stage disease models, but the clinical trials included advanced PD patients. To conclude the value of NTF therapies, clinical studies should be performed in early‐stage patients with prodromal symptoms, that is, before motor manifestations. In this review, we summarize currently available diagnostic and prognostic biomarkers that could help identify at‐risk patients benefiting from NTF therapies. Focus is on biochemical and imaging biomarkers, but also other modalities are discussed. Neuroimaging is the most important diagnostic tool today, but α‐syn imaging is not yet viable. Modern techniques allow measuring various forms of α‐syn in cerebrospinal fluid, blood, saliva, and skin. Digital biomarkers and artificial intelligence offer new means for early diagnosis and longitudinal follow‐up of degenerative brain diseases.