Deepak Kumar, Snehasish Shee, Ashok Kumar Datusalia, Shyam Sunder Sharma
Parkinson's disease (PD) and Alzheimer's disease (AD) are the most prevalent neurodegenerative disorders and represent a major global health burden. Despite distinct clinical features, both diseases share key pathogenic mechanisms, particularly oxidative stress and mitochondrial dysfunction, which contribute to neuronal injury and progression. Current diagnostic approaches based on clinical evaluation, neuroimaging, and cerebrospinal fluid (CSF) biomarkers are invasive, costly, and often detect disease only after significant neuronal loss, underscoring the need for minimally invasive, pathway-relevant assays. This chapter reviews blood- and CSF-based biomarker assays reflecting oxidative stress and mitochondrial dysfunction in PD and AD, including lipid peroxidation products, antioxidant capacity, oxidative DNA damage markers, mitochondrial bioenergetic indices, and quality-control proteins. Emerging assay platforms targeting circulating cell-free mitochondrial DNA, mitochondrial-derived vesicles, extracellular vesicle cargo, and regulatory non-coding RNAs are also discussed. The mechanistic relevance of these biomarkers is examined in relation to impaired mitochondrial quality control, disrupted redox homeostasis, defective oxidative phosphorylation, and interactions with disease-defining proteins such as α-synuclein, amyloid-β, and phosphorylated tau. Collectively, these assay-based biomarkers hold promise for early detection, disease monitoring, and therapeutic stratification, although challenges related to standardization, sensitivity, and longitudinal validation remain.