Dorsal motor nucleus of vagus protein aggregates in Lewy body disease with autonomic dysfunction.
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 alphasynuclein, 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. alphaSynuclein, 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 alphasynuclein and tau aggregation (p<0.05) and between DMV alphasynuclein and the patients' UPDRS scores (p<0.05) suggesting incremental DMV degeneration with disease progression. However, there was no correlation between DMV alphasynuclein, 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.
Miller
Veronica M
VM
Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, UK. vmiller@wadsworth.org
Kenny
Rose Anne
RA
Oakley
Arthur E
AE
Hall
Ros
R
Kalaria
Rajesh N
RN
Allan
Louise M
LM
D000368:Aged; D000369:Aged, 80 and over; D001342:Autonomic Nervous System Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D005455:Fluorescent Antibody Technique; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000473:pathology*; D020961:Lewy Body Disease / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D025801:Ubiquitin / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
D055551:HSP27 Heat-Shock Proteins; D025801:Ubiquitin; D051844:alpha-Synuclein; D016875:tau Proteins