ABSTRACT
INTRODUCTION Disorders Characterized by α-Synuclein Pathology α-Synucleinopathy is a generic term used to describe a heterogeneous group of neurodegenerative disorders including Parkinson’s disease (PD), PD and dementia (PDD), dementia with Lewy bodies (DLB) (1), and multiple system atrophy (MSA) (2,3). Postmortem, these diseases have abundant α-synuclein inclusions within the brain, but the cellular and anatomical distribution of pathology is quite different (4). PD, PDD, and DLB are often considered an overlapping spectrum of disorders; however, there is little practical benefit (5,6). Each has a distinct clinical presentation, disease course, and response to therapeutic medication. Pathologically, PD is characterized neuronal loss and depigmentation of the substantia nigra, with Lewy body inclusions within surviving neurons in the brain stem (7,8). These are generally spherical in the perikarya, ∼15 mm in diameter, with a dense, granular core surrounded by a radiating rim of 8-10 nm α-synuclein filaments (9). Intraneuritic Lewy bodies are also commonly found within cell processes of the dorsal motor nucleus of the vagus and in the basal nucleus of Meynert. Neocortical Lewy bodies and Lewy neurites are infrequent. Staging criteria have recently been proposed but have yet to be validated (7,8).
