Pathological correlates of gastrointestinal dysfunction in Parkinson's disease

Abstract

Gastrointestinal dysfunction is a prominent manifestation of Parkinson's disease (PD). Gastrointestinal symptoms in PD include reduced salivation, dysphagia, impaired gastric emptying, constipation, and defecatory dysfunction. Constipation may precede the development of somatic motor symptoms of PD for several years. Neuropathological studies show early accumulation of abnormal alpha-synuclein (α-SYN) containing inclusions (Lewy neurites) in the enteric nervous system (ENS) and dorsal motor nucleus of the vagus (DMV) both in PD and in incidental Lewy body disease (ILBD). These findings provided the basis for the hypothesis that α-SYN pathology progresses in a centripetal, prion-like fashion, from the ENS to the DMV and then to more rostral areas of the central nervous system. Colonic biopsies may show accumulation α-SYN immunoreactive Lewy neurites in the submucosal plexus of PD patients. Salivary gland involvement is prominent in PD and α-SYN pathology can be detected both at autopsy and in minor salivary gland biopsies.