Neuropathology of Nonmotor Symptoms of Parkinson's Disease

Parkinson's disease (PD), a multiorgan neurodegenerative disorder associated with α-synuclein deposits throughout the nervous system and many organs, is clinically characterized by motor and nonmotor features, many of the latter antedating motor dysfunctions by 20 or more years. The causes of the nonmotor manifestations such as olfactory, autonomic, sensory, neuropsychiatric, visuospatial, sleep, and other disorders are unlikely to be related to single lesions. They are mediated by the involvement of both dopaminergic and nondopaminergic systems, and diverse structures outside the nigrostriatal system that is mainly responsible for the motor features of PD. The nonmotor alterations appear in early/prodromal stages of the disease and its further progression, suggesting a topographical and chronological spread of the lesions. This lends further support for the notion that PD is a multiorgan proteinopathy, although the exact relationship between presymptomatic and later developing nonmotor features of PD and neuropathology awaits further elucidation.