title: Pathologic accumulation of α-synuclein and Aβ in Parkinson disease patients with dementia.
abstract: OBJECTIVE
  To determine the relative contributions of individual pathologic protein deposits associated with dementia in patients with Parkinson disease (PD).
  
  
  METHODS
  Autopsied patients were analyzed from February 24, 2005, through July 25, 2010, to determine the distribution and severity of individual pathologic protein deposits (α-synuclein, Aβ, and tau) using routine protocols for histologic and immunohistochemical analysis and established neuropathologic staging criteria. Clinical data were extracted from an electronic medical record system used for all patients with PD.
  
  
  METHODS
  Thirty-two consecutive autopsied patients treated at the Washington University Movement Disorders Center who had neuropathologic confirmation of PD and a history of dementia, regardless of the timing of the onset of dementia with respect to motor symptoms.
  
  
  RESULTS
  Three pathologic subgroups of dementia associated with PD were identified: (1) predominant synucleinopathy (Braak Lewy body stages 5-6) (12 [38%]), (2) predominant synucleinopathy with Aβ deposition (Braak amyloid stages B-C) but minimal or no cortical tau deposition (19 [59%]), and (3) synucleinopathy and Aβ deposition with at least moderate neocortical tauopathy (Braak tau stages 5-6; 1 [3%]). Kaplan-Meier and Cox regression analyses revealed that patients with synucleinopathy plus Aβ deposition had significantly shorter survival (years from PD onset until death and years from dementia onset until death) than patients with synucleinopathy only.
  
  
  CONCLUSIONS
  Dementia associated with PD has 2 major pathologic subgroups: neocortical synucleinopathy and neocortical synucleinopathy with Aβ deposition. Alzheimer disease with neocortical Aβ and tau deposition does not commonly cause dementia with PD. Furthermore, accumulation of Aβ is associated with lower survival rates in PD patients with dementia. Additional studies are needed to prospectively determine the association between α-synuclein and Aβ accumulation and the role of Aβ in the development and progression of cognitive impairment in PD.
authors: Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, MO 63110, USA. kotzbauerp@wustl.edu
authors: Paul T
authors: PT
authors: Kotzbauer
authors: Nigel J
authors: NJ
authors: Cairns
authors: Meghan C
authors: MC
authors: Campbell
authors: Allison W
authors: AW
authors: Willis
authors: Brad A
authors: BA
authors: Racette
authors: Samer D
authors: SD
authors: Tabbal
authors: Joel S
authors: JS
authors: Perlmutter
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001344:Autopsy; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D003704:Dementia / Q000150:complications / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000150:complications / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D012044:Regression Analysis; D012189:Retrospective Studies; D018709:Statistics, Nonparametric; D051844:alpha-Synuclein / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D051844:alpha-Synuclein; D016875:tau Proteins