Autonomic involvement in Parkinson's disease: Pathology, pathophysiology, clinical features and possible peripheral biomarkers

Autonomic nervous system involvement occurs at early stages in both Parkinson's disease (PD) and incidental Lewy body disease (ILBD), and affects the sympathetic, parasympathetic, and enteric nervous systems (ENS).It has been proposed that alpha-synuclein (α-SYN) pathology in PD has a distal to proximal progression along autonomic pathways. The ENS is affected before the dorsal motor nucleus of the vagus (DMV), and distal axons of cardiac sympathetic nerves degenerate before there is loss of paravertebral sympathetic ganglion neurons. Consistent with neuropathological findings, some autonomic manifestations such as constipation or impaired cardiac uptake of norepinephrine precursors, occur at early stages of the disease even before the onset of motor symptoms. Biopsy of peripheral tissues may constitute a promising approach to detect α-SYN neuropathology in autonomic nerves and a useful early biomarker of PD.