Dorsal Motor Nucleus of Vagus protein aggregates in Lewy Body Disease with autonomic dysfunction

Abstract

The Dorsal Motor Nucleus of Vagus (DMV) is degenerated in many patients with early stage Lewy Body Diseases (LBD). Many patients with LBD also develop symptomatic autonomic dysfunction prior to motor and cognitive symptoms. The DMV, along with the Nucleus Ambiguous (NA) and Raphe Obscurus (RO) regulates a variety of autonomic reflexes, suggesting that there may be an association between the degree of neurodegenerative protein aggregation in the DMV and symptomatic autonomic dysfunction in patients with LBD. Using digital in vivo pathology, we quantified αsynuclein, tau, ubiquitin and Heat Shock Protein 27 (HSP27) containing neurons in the DMV, NA, RO, in addition to the hypoglossal nucleus in 12 LBD patients. αSynuclein, ubiquitin and tau aggregates most greatly affected the DMV followed by the NA, RO, but never the hypoglossal nucleus. There was a positive correlation between DMV αsynuclein and tau aggregation ( p < 0.05) and between DMV αsynuclein and the patients' UPDRS scores ( p < 0.05) suggesting incremental DMV degeneration with disease progression. However, there was no correlation between DMV αsynuclein, tau, ubiquitin or HSP27 density and the patient's autonomic dysfunction scores. The specific incremental nature of degeneration in the DMV, suggests that by characterizing region specific molecular mechanisms underpinning DMV as opposed to NA degeneration in LBD, the pathogenesis of the disorder may be better understood. Whether DMV degeneration is causative of symptomatic autonomic dysfunction in LBD remains to be determined.