Advances in Diagnosis and Prognosis of Parkinson Disease

Abstract

The biological definition of Parkinson disease (PD) is still an open issue. Indeed, PD represents a heterogeneous disorder in which clinical symptoms may correspond to different biological substrates. In vivo biological characterization of PD is of great importance, to formulate an accurate diagnosis in the early stages of the disease, when clinical symptoms may be uncertain and disease-modifying therapies may have the greatest chance to halt disease progression. In recent years, several advances have been made in the field of fluid biomarkers. Among these, α-synuclein amplification assays (αS-SAAs) in CSF can detect the presence of α-synucleinopathy, the most widely recognized biological feature of PD.1,2 However, αS-SAAs are not yet quantitative, the extracted kinetic features poorly associate with clinical scores, and they do not capture alterations other than α-synucleinopathy that occur in patients with PD (e.g., neuroinflammation, synaptic damage, mitochondrial and autophagic dysfunctions). Moreover, some genetic forms of PD, such as LRKK2-PD, may not be characterized by α-synucleinopathy, and this may explain αS-SAA's poor sensitivity.2