Pathophysiology of synuclein aggregation in Lewy body disease

We provide an overview of synaptic pathology in dementia with Lewy bodies (DLB) and related neurodegenerative disorders that are characterised by intraneuronal accumulation of α-synuclein aggregates. The review addresses the clinico-neuropathological correlates of synaptic pathology in Lewy body disease, and concentrates on: altered α-synuclein metabolism, mechanisms leading to α-synuclein fibril formation (self-polymerisation, α-synuclein mutations and post-translational modifications) and how these influence the axonal transport and synaptic network in ageing and disease process. Understanding the mechanisms leading to intraneuronal α-synuclein accumulation are crucial for the development of novel therapies for treatment of Lewy body disease.