title: Lewy- and Alzheimer-type pathologies in midbrain and cerebellum across the Lewy body disorders spectrum.
abstract: Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are pathologically characterized by intraneuronal α-synuclein aggregates and thus labelled as Lewy body disorders (LBD). Conjoint cortical α-synuclein, tau and amyloid-β (Aβ), and striatal Aβ aggregates, have been related to dementia in LBD. Interpretation of current and emerging in vivo molecular imaging of these pathologies will need of precise knowledge of their topographic distribution. We aimed to assess these pathologies further down the encephalon across the LBD-spectrum.
  
  
  
  Semiquantitative rating of α-synuclein, Aβ and hyperphosphorylated tau aggregates in midbrain (and cerebellum in the case of Aβ as it represents the last β-amyloidosis stage) sections from cases representative of the LBD-spectrum (PD non-dementia, PD-dementia, DLB; n = 10 each) compared to controls (n = 10) and Alzheimer's disease (AD; n = 10).
  
  
  
  α-synuclein midbrain scores rose from controls to AD and then LBD irrespective of dementia. Aβ and tau were more prominent in the tectum/tegmentum, increasing from controls to LBD (mostly in dementia cases in the case of Aβ), and then peaking in AD. By contrast, cerebellar Aβ scores were marginal across the LBD-spectrum, as opposed to AD, only showing a trend towards greater involvement in LBD cases with dementia.
  
  
  
  Frequency and severity of Aβ and tau pathologies in the midbrain across the LBD-spectrum were midway between controls and AD, with Aβ in the tectum/tegmentum being associated with dementia. These findings might have potential implications in the eventual interpretation of regional uptake of in vivo molecular imaging of these pathologies.
authors.affiliation: Parkinson's disease and Movement Disorders Unit, Neurology Service, IDIBAPS, CIBERNED, Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain.|Service of Neurology, Hospital Universitario Marqués de Valdecilla (IFIMAV), University of Cantabria (UC), Santander, Cantabria, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Sierra
authors.affiliation: Neurological Tissue Bank of the Biobanc-Hospital Clinic-IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Catalonia, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Gelpi
authors.affiliation: Parkinson's disease and Movement Disorders Unit, Neurology Service, IDIBAPS, CIBERNED, Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Martí
authors.affiliation: Parkinson's disease and Movement Disorders Unit, Neurology Service, IDIBAPS, CIBERNED, Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain.
authors.forename: Y
authors.initials: Y
authors.lastname: Compta
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D016631:Lewy Bodies / Q000378:metabolism / Q000473:pathology; D020961:Lewy Body Disease / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008636:Mesencephalon / Q000378:metabolism / Q000473:pathology*; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology; D051844:alpha-Synuclein / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D051844:alpha-Synuclein; D016875:tau Proteins
keywords: Lewy body disorders spectrum; amyloid-β; cerebellum; hyperphosphorylated tau; midbrain; α-synuclein