CONTENTS -- 1 Prologue -- 1.1 sPD and Parkinsonism -- 1.2 sPD Is a Proteinopathy Linked to the Development of Abnormal Intraneuronal Inclusions (Lewy Pathology: Lewy Neurites, Lewy bodies, Lewy plaques) -- 2 Morphology of Lewy Pathology -- 2.1 The Protein α-Synuclein -- 2.2 Protein Misfolding and Abnormal Aggregation of α-Synuclein -- 2.3 Light Microscopic Visualization of Lewy Pathology -- 2.3.1 Lewy Neurites -- 2.3.2 Granular Aggregations -- 2.3.3 Pale Bodies and Lewy Bodies -- 2.3.4 Lewy Plaques -- 2.4 Degradation of Lewy Pathology -- 2.5 Lewy Pathology Can Co-occur with Pathology Related to Other Disorders -- 3 The Evolving Distribution Pattern of Lewy Pathology Associated with sPD Renders Neuropathological Staging Possible -- 3.1 Incidental Lewy Pathology -- 3.2 Presymptomatic and Symptomatic Phases -- 3.3 Vulnerable Regions are Interconnected Anatomically -- 4 Stage 1 -- 4.1 Pathology in Olfactory Structures -- 4.2 Basic Organization of the Medullary Autonomic Region -- 4.3 Involvement of Preganglionic Parasympathetic Projection Neurons -- 4.4 Pathology in the Enteric Nervous System -- 4.5 Is sPD Inducible by a Neurotropic Pathogen Akin to a Slow Virus? -- 4.6 Involvement of Preganglionic and Postganglionic Sympathetic Projection Neurons -- 4.7 Pathology in Lamina I of the Spinal Cord -- 5 Stage 2 -- 5.1 Involvement of the Medulla Oblongata and Pontine Tegmentum -- 5.2 Basic Organization of the Gain Setting System -- 5.2.1 Lower Raphe Nuclei -- 5.2.2 Magnocellular Reticular Nuclei -- 5.2.3 Coeruleus-Subcoeruleus Complex -- 5.3 Potential Functional Consequences of the Lesions -- 6 Stage 3 -- 6.1 Involvement of the Mesencephalic Tegmentum and Basal Forebrain -- 6.1.1 Central Subnucleus of the Amygdala -- 6.1.2 Substantia Nigra and Adjoining Nuclei -- 6.2 Basic Organization of Nonthalamic Nuclei with Diffuse Projections.

6.2.1 Magnocellular Nuclei of the Basal Forebrain -- 6.2.2 Pedunculopontine Tegmental Nucleus -- 6.2.3 Tuberomamillary Nucleus -- 6.2.4 Upper Raphe Nuclei -- 6.3 Potential Functional Consequences of the Lesions -- 7 Stage 4 -- 7.1 Involvement of the Amygdala and Thalamus -- 7.1.1 Amygdala -- 7.1.2 Thalamus -- 7.2 Basic Organization of the Cerebral Cortex and Limbic Circuit -- 7.2.1 Allocortex and Neocortex -- 7.2.2 Mesocortex -- 7.2.3 Limbic Circuit -- 7.3 Involvement of the Temporal Mesocortex and Hippocampal Formation -- 7.3.1 Temporal Mesocortex -- 7.3.2 Hippocampal Formation -- 7.4 Involvement of Insular, Subgenual, and Anterior Cingulate Areas -- 7.5 Potential Functional Consequences of the Lesions -- 8 Stages 5 and 6 -- 8.1 Involvement of Neocortex and Basal Ganglia -- 8.1.1 Neocortex -- 8.1.2 Basal Ganglia -- 8.2 Basic Organization of the Basal Ganglia and Striatal Circuit -- 8.2.1 Striatum -- 8.2.2 Pallidum -- 8.2.3 Subthalamic Nucleus -- 8.2.4 Claustrum -- 8.3 Dot-Like Inclusions and Abnormally Altered Astrocytes in the Forebrain -- 8.4 Disruption of the Striatal Circuit -- 8.5 Potential Functional Consequences of Lesions -- 8.6 Pathologically Changed Components of the Cerebellar Circuit -- 9 The Progression of the Cortical Lesions Mimics the Pattern of Myelination in Reverse Order -- 10 The Staging Hypothesis: Assumptions, Challenges, Potential.