title: Neuropathological analysis of brainstem cholinergic and catecholaminergic nuclei in relation to rapid eye movement (REM) sleep behaviour disorder.
abstract: OBJECTIVE
  Rapid eye movement sleep behaviour disorder (RBD) is characterized by loss of muscle atonia during rapid eye movement sleep and is associated with dream enactment behaviour. RBD is often associated with α-synuclein pathology, and we examined if there is a relationship of RBD with cholinergic neuronal loss in the pedunculopontine/laterodorsal tegmental nucleus (PPN/LDT), compared to catecholaminergic neurones in a neighbouring nucleus, the locus coeruleus (LC).
  
  
  METHODS
  This retrospective study utilized human brain banked tissues of 11 Lewy body disease (LBD) cases with RBD, 10 LBD without RBD, 19 Alzheimer's disease (AD) and 10 neurologically normal controls. Tissues were stained with choline acetyl transferase immunohistochemistry to label neurones of PPN/LDT and tyrosine hydroxylase for the LC. The burden of tau and α-synuclein pathology was measured in the same regions with immunohistochemistry.
  
  
  RESULTS
  Both the LC and PPN/LDT were vulnerable to α-synuclein pathology in LBD and tau pathology in AD, but significant neuronal loss was only detected in these nuclei in LBD. Greater cholinergic depletion was found in both LBD groups, regardless of RBD status, when compared with normals and AD. There were no differences in either degree of neuronal loss or burden of α-synuclein pathology in LBD with and without RBD.
  
  
  CONCLUSIONS
  Whether decreases in brainstem cholinergic neurones in LBD contribute to RBD is uncertain, but our findings indicate these neurones are highly vulnerable to α-synuclein pathology in LBD and tau pathology in AD. The mechanism of selective α-synuclein-mediated neuronal loss in these nuclei remains to be determined.
authors.affiliation: Department of Pathology and Neuroscience Psychology, Mayo Clinic, Jacksonville, FL 32224, USA.
authors.forename: B N
authors.initials: BN
authors.lastname: Dugger
authors.forename: M E
authors.initials: ME
authors.lastname: Murray
authors.forename: B F
authors.initials: BF
authors.lastname: Boeve
authors.forename: J E
authors.initials: JE
authors.lastname: Parisi
authors.forename: E E
authors.initials: EE
authors.lastname: Benarroch
authors.forename: T J
authors.initials: TJ
authors.lastname: Ferman
authors.forename: D W
authors.initials: DW
authors.lastname: Dickson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001933:Brain Stem / Q000378:metabolism / Q000473:pathology*; D002395:Catecholamines / Q000378:metabolism*; D018678:Cholinergic Agents / Q000378:metabolism*; D005260:Female; D006801:Humans; D020961:Lewy Body Disease / Q000175:diagnosis / Q000473:pathology; D008125:Locus Coeruleus / Q000378:metabolism; D008297:Male; D009422:Nervous System Diseases / Q000175:diagnosis / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D020187:REM Sleep Behavior Disorder / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D012189:Retrospective Studies; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D002395:Catecholamines; D018678:Cholinergic Agents; D051844:alpha-Synuclein