Blood-based biomarkers in Alzheimer's and Parkinson's disease: From molecular pathology to therapeutic potential.

Abstract

Alzheimer's (AD) and Parkinson's disease (PD) represent a major class of neurodegenerative disorders characterized by different proteinopathies with amyloid-β plaques and tau tangles in AD, while α-synuclein containing Lewy bodies in PD, specific molecular signatures. Alongside this central mechanism, they share pathological cascades including axonal degeneration, synaptic dysfunction, glial activation and neuroinflammation. The emergence of blood-based biomarkers, represents a paradigm shift in the field of diagnosis and therapeutics by addressing these core pathological mechanism of central nervous system. This chapter highlights a overview of blood-based biomarkers emerging in the field of AD and PD, exploring the clinical utility of core pathology markers (Aβ42/40, p-tau species, and α-synuclein), alongside other neurodegenerative markers such as neurofilament light chain and glial activation markers like GFAP. Beyond the diagnosis, we emphasize on the potential role of blood-based biomarkers as a surrogate and pharmacodynamic endpoint in disease modifying clinical trial development, facilitating dose optimization and target engagement. Future prospects empathize on the use of multimodal approach integration, trajectory modeling and novel target discovery. Collectively, these blood-based biomarkers enable transition of neurodegenerative disorders treatment from symptom-based classification to towards a mechanism targeted therapeutic framework.