Fluid biomarkers for Lewy body disease ―An overview of recent advances in fluid biomarkers, including RT–QuIC, for Lewy body disease―

Abstract

α–Synucleinopathies, including Parkinson Disease (PD), Multiple System Atrophy (MSA), and Lewy Body Dementia (DLB), are characterized by the pathological accumulation of misfolded α–synuclein (α–syn) aggregates. Recent advancements in fluid biomarkers, particularly α–syn seed amplification assays (SAA), have opened new avenues for early and precise diagnosis. Real–Time Quaking–induced Conversion (RT–QuIC) and similar assays have demonstrated high sensitivity and specificity in detecting α–syn seeds in cerebrospinal fluid (CSF) and blood, correlating with clinical subtypes and progression stages. Additionally, efforts to integrate biomarkers such as α–syn SAA with imaging techniques and genetic markers are shaping a biological classification and staging framework for PD and related disorders. However, challenges persist, including variability in assay protocols, substrate preparation, and interference from biological matrices in blood–based assays. Emerging technologies, such as Nano–QuIC, aim to address these issues by enhancing detection sensitivity and specificity. The continued refinement of biomarker assays promises to revolutionize diagnostic accuracy, facilitate early therapeutic intervention, and provide critical insights into the molecular mechanisms underlying α–synucleinopathies.