title: The significance of α-synuclein, amyloid-β and tau pathologies in Parkinson's disease progression and related dementia.
abstract: BACKGROUND
  Dementia is one of the milestones of advanced Parkinson's disease (PD), with its neuropathological substrate still being a matter of debate, particularly regarding its potential mechanistic implications.
  
  
  OBJECTIVE
  The aim of this study was to review the relative importance of Lewy-related α-synuclein and Alzheimer's tau and amyloid-β (Aβ) pathologies in disease progression and dementia in PD.
  
  
  METHODS
  We reviewed studies conducted at the Queen Square Brain Bank, Institute of Neurology, University College London, using large PD cohorts.
  
  
  RESULTS
  Cortical Lewy- and Alzheimer-type pathologies are associated with milestones of poorer prognosis and with non-tremor predominance, which have been, in turn, linked to dementia. The combination of these pathologies is the most robust neuropathological substrate of PD-related dementia, with cortical Aβ burden determining a faster progression to dementia.
  
  
  CONCLUSIONS
  The shared relevance of these pathologies in PD progression and dementia is in line with experimental data suggesting synergism between α-synuclein, tau and Aβ and with studies testing these proteins as disease biomarkers, hence favouring the eventual testing of therapeutic strategies targeting these proteins in PD.
authors.affiliation: Parkinson Disease and Movement Disorders Unit, Neurology Service, IDIBAPS, CIBERNED, Hospital Clínic, Barcelona, Spain.
authors.forename: Yaroslau
authors.initials: Y
authors.lastname: Compta
authors.forename: Laura
authors.initials: L
authors.lastname: Parkkinen
authors.forename: Peter
authors.initials: P
authors.lastname: Kempster
authors.forename: Mariana
authors.initials: M
authors.lastname: Selikhova
authors.forename: Tammaryn
authors.initials: T
authors.lastname: Lashley
authors.forename: Janice L
authors.initials: JL
authors.lastname: Holton
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lees
authors.forename: Tamas
authors.initials: T
authors.lastname: Revesz
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003704:Dementia / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D006801:Humans; D010300:Parkinson Disease / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D012189:Retrospective Studies; D051844:alpha-Synuclein / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D051844:alpha-Synuclein; D016875:tau Proteins
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