title: Medullary autonomic pathology in carotid sinus hypersensitivity.
abstract: OBJECTIVE
  Carotid sinus hypersensitivity (CSH) is an ageing-related autonomic disorder, rarely occurring before the age of 50 years but increasing in incidence thereafter. Clinical symptoms of CSH include falls and dizziness, thought to be precipitated by dysfunctional baroreflex responses. CSH is highly prevalent in Alzheimer's disease (AD), Parkinson's disease (PD) and dementia with Lewy bodies (DLB); diseases that are associated with variable degeneration of medullary autonomic nuclei which regulate baroreflex responses. Currently, there are no descriptions of the integrity of medullary autonomic nuclei in CSH. We hypothesized medullary autonomic degeneration is found in elderly patients with CSH.
  
  
  METHODS
  Using in vitro digital imaging, we quantified the burden of tau, amyloid beta and alpha-synuclein in autonomic nuclei of 12 patients prospectively assessed with CSH (age 83 years) compared with 14 (80 years) control subjects.
  
  
  RESULTS
  We found increased tau (P < 0.000) accumulation in baroreflex associated nuclei, but not the hypoglossal or raphe in the CSH patients. Medullary tau accumulation was not related to the development of AD in the CSH patients. Tau was colocalized to catecholaminergic neurones and occurred in the absence of neuronal loss. We found no difference in alpha-synuclein, amyloid beta or microglial numbers between the CSH cases and controls.
  
  
  CONCLUSIONS
  We suggest that hyperphosphorylated tau accumulation particularly in tyrosine hydroxylase containing neurones may impair central regulation of baroreflex responses in patients with CSH. Future clinic-pathological investigations should reveal whether medullary degeneration is the cause of CSH symptoms.
authors.affiliation: Institute for Ageing and Health, Neurovascular Research Unit, Sir James Spence Institute, Royal Victoria Infirmary, Wolfson Research Centre, Newcastle General Hospital, Newcastle Upon Tyne, UK. veronica.miller2@mail.dcu.ie
authors.forename: V M
authors.initials: VM
authors.lastname: Miller
authors.forename: R A
authors.initials: RA
authors.lastname: Kenny
authors.forename: J Y
authors.initials: JY
authors.lastname: Slade
authors.forename: A E
authors.initials: AE
authors.lastname: Oakley
authors.forename: R N
authors.initials: RN
authors.lastname: Kalaria
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism; D002102:Cadaver; D002346:Carotid Sinus / Q000473:pathology*; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000473:pathology*; D016631:Lewy Bodies / Q000473:pathology; D008297:Male; D008526:Medulla Oblongata / Q000473:pathology*; D017628:Microglia / Q000473:pathology; D009474:Neurons / Q000473:pathology; D012016:Reference Values; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016875:tau Proteins