Protein misfolding and aggregation and its role in dementia with Lewy bodies

Abstract

Dementia with Lewy bodies (DLB) is a progressive neurodegenerative disorder characterized by the accumulation of misfolded α-synuclein within Lewy bodies, leading to widespread neuronal dysfunction. Protein misfolding and aggregation serve as key pathological mechanisms, influenced by genetic mutations, as well as environmental triggers like toxins and infections. The interplay between α-synuclein and other neurodegenerative pathways, particularly tau and amyloid-β, exacerbates disease progression. Advances in biomarker research, including neuroimaging and fluid-based assays, are enhancing early detection, while emerging therapeutic strategies focus on molecular chaperones, autophagy enhancement, and gene-editing approaches. Understanding the mechanisms of protein misfolding in DLB not only improves diagnostic accuracy but also provides potential avenues for disease-modifying therapies. Ongoing research offers promising prospects for targeted interventions, bridging the gap between pathophysiological insights and clinical applications in neurodegenerative disorders. © 2026 Elsevier Inc. All rights reserved..