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 (a-syn) in the brain. The symptomatic
treatment is started after the onset of motor manifestations in a late
stage of the disease. Preclinical studies show promising results of
disease-modifying neuroprotective or even neurorestorative therapies
with neurotrophic factors (NTFs). Three NTFs have entered phase I-II
clinical trials with inconclusive outcomes. This is not surprising since
the preclinical evidence is from acute early-stage disease models but
the clinical trials included advanced PD patients. In order to conclude
the value of NTF therapies, clinical studies should be performed in
early-stage patients with prodromal symptoms, i.e. 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 a-syn
imaging is not yet viable. Modern techniques allow measuring various
forms of a-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.