Autonomic dysfunction in neurodegenerative disease

Abstract

In addition to their more studied cognitive and motor effects, neurodegenerative diseases are also associated with impairments in autonomic function — the regulation of involuntary physiological processes. These autonomic impairments manifest in different ways and at different stages depending on the specific disease. The neural networks responsible for autonomic regulation in the brain and body have characteristics that render them particularly susceptible to the prion-like spread of protein aggregation involved in neurodegenerative diseases. Specifically, the axons of these neurons — in both peripheral and central networks — are long and poorly myelinated axons, which make them preferential targets for pathological protein aggregation. Moreover, cortical regions integrating information about the internal state of the body are highly connected with other brain regions, which increases the likelihood of intersection with pathological pathways and prion-like spread of abnormal proteins. This leads to an autonomic ‘signature’ of dysfunction, characteristic of each neurodegenerative disease, that is linked to the affected networks and regions undergoing pathological aggregation.