Peripheral manifestations of nigrostriatal neurodegeneration in Parkinson's disease

Parkinson's disease (PD), a neurodegenerative condition, is characterized by dysfunction of dopaminergic pathways leading to prominent movement and non-movement disorders, including cognitive decline and memory loss. The clinical symptoms of PD progressively worsen over time, and there is no precise confirmatory laboratory test for early diagnosis. Although abnormal neuroimaging signatures and changes in cerebrospinal fluid represent significant diagnostic value, their limited accessibility, high cost, and invasiveness restrict their clinical applications. As a potential alternative, blood-borne biomarkers represent a feasible and adaptable indicator, as blood sample collection is minimally invasive, cost-effective, suitable for large-scale populations, and permits repeated sampling for disease diagnosis and monitoring. Notably, altered cellular and biochemical composition of circulating blood can reflect pathogenic changes involved in many diseases, including PD. Abnormal levels of circulating α-synuclein, factors related to chronic inflammation, oxidative damage, impaired mitochondrial function, and neuronal injury in the blood are considered potential biomarkers of PD. This chapter provides an overview of blood biomarkers that aid in predicting the pathogenic state of PD. Various categories of biomarkers, including protein aggregates, inflammation-related factors, oxidative stress markers, metabolomic and lipidomic signatures, genetic and epigenetic status, and PD-related exosomes are discussed. These blood biomarkers could serve as a diagnostic tool for PD and may provide predictive measures of disease outcomes, as well as neurobiological correlates of brain changes, thereby offering valuable indications for treatment strategies.