title: Brain stem pathology in Parkinson's disease: an evaluation of the Braak staging model.
abstract: The lower brain stem of 25 pathologically-confirmed Parkinson's disease (PD) cases was examined by alpha synuclein immunohistochemistry to characterize pathological accumulation of alpha synuclein (Lewy-type α-synucleinopathy, LTS) in the medulla oblongata, to examine differences between affected regions and test a proposed model of staging of pathology in PD. All cases had LTS in the medulla, including the dorsal motor nucleus of the vagus (dmX), when present. The distribution followed a consistent pattern and appeared to be concentrated in a tyrosine hydroxylase (TH) immunoreactive region, probably representing the dorsal IX/X nuclear complex and the intermediate reticular zone. LTS density was greatest in the dmX. A similar distribution pattern to PD was seen in 14 incidental Lewy body disease (ILBD) cases, five derived from the Queen Square Brain Bank tissue collection and nine identified in separate series of 60 neurologically-normal individuals, and in three cases with the G2019S mutation of LRRK2. Semiquantitative assessment showed that severity of pathology in the dmX was not correlated with the severity of cortical pathology. Semiquantitative assay of TH and ChAT peptide expression in the medulla showed that TH expression in PD and ILBD did not differ from controls. These findings broadly support the Braak hypothesis of caudo-rostral development but indicate that the extent of the disease in the cortex and the severity of pathology in the medulla were independent of one another.
authors.affiliation: Reta Lila Weston Institute of Neurological Studies, UCL, Institute of Neurology, London, United Kingdom. a.kingsbury@ion.ucl.ac.uk
authors.forename: Ann E
authors.initials: AE
authors.lastname: Kingsbury
authors.forename: Rina
authors.initials: R
authors.lastname: Bandopadhyay
authors.forename: Laura
authors.initials: L
authors.lastname: Silveira-Moriyama
authors.forename: Hilary
authors.initials: H
authors.lastname: Ayling
authors.forename: Constantinos
authors.initials: C
authors.lastname: Kallis
authors.forename: William
authors.initials: W
authors.lastname: Sterlacci
authors.forename: Hans
authors.initials: H
authors.lastname: Maeir
authors.forename: Werner
authors.initials: W
authors.lastname: Poewe
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lees
mesh_terms: D000368:Aged; D001933:Brain Stem / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016631:Lewy Bodies / Q000378:metabolism / Q000473:pathology; D020961:Lewy Body Disease / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D016017:Odds Ratio; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology*; D012720:Severity of Illness Index; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D051844:alpha-Synuclein; D014446:Tyrosine 3-Monooxygenase