title: Apomorphine: A potential modifier of amyloid deposition in Parkinson's disease?
abstract: Evidence from clinical and pathological studies suggests a role for both alpha-synuclein and amyloid-beta in the pathophysiology of dementia associated with PD. Recent work demonstrated improvement in memory and reduced amyloid-beta burden in transgenic murine Alzheimer's models given subcutaneous apomorphine. The aim of this work was to determine whether antemortem exposure to apomorphine was associated with lower levels of amyloid-beta in brain tissue in a clinicopathological study of PD.
  
  
  
  The case notes of donors with pathologically proven PD who had (n = 36) and had not received apomorphine (n = 35) during life for motor complications were reviewed to determine presence or absence of cognitive impairment. The four groups were well matched for disease duration, age at death, sex, and apolipoprotein E4 genotype. The severity of amyloid-beta mature/diffuse plaque load, tau pathology, and alpha-synuclein pathology were all established. Cerebral amyloid angiopathy was determined based on a four-tier grading system.
  
  
  
  Within the cognitively normal cases, significantly reduced amyloid-beta deposition was present in those with antemortem apomorphine exposure; this finding was not replicated in those with cognitive impairment plus previous apomorphine use. In the apomorphine cognitively normal group only, a significant negative association was observed between maximum apomorphine dose received and amyloid-beta burden. Early and maximum doses of apomorphine plus apolipoprotein genotype and sex were significant predictors of total plaque load in an explanatory model.
  
  
  
  This exploratory study suggests that apomorphine may have a modifying effect on amyloid deposition in nondemented PD cases and thus may represent a potential therapy to reduce cognitive impairment in PD. © 2015 Movement Disorder Society.
authors.affiliation: Institute of Neuroscience, Newcastle University, Newcastle, United Kingdom.
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Yarnall
authors.affiliation: The Queen Square Brain Bank for Neurological Disorders, Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom.
authors.forename: Tammaryn
authors.initials: T
authors.lastname: Lashley
authors.affiliation: Reta Lila Weston Institute of Neurological Studies, University College London, United Kingdom.
authors.forename: Helen
authors.initials: H
authors.lastname: Ling
authors.affiliation: The Queen Square Brain Bank for Neurological Disorders, Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom.|Reta Lila Weston Institute of Neurological Studies, University College London, United Kingdom.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lees
authors.affiliation: Industrial Statistics Research Unit, Newcastle University, Newcastle, United Kingdom.
authors.forename: Shirley Y
authors.initials: SY
authors.lastname: Coleman
authors.affiliation: Cork University Hospital, Cork, Ireland.
authors.forename: Sean S
authors.initials: SS
authors.lastname: O'Sullivan
authors.affiliation: Parkinson Disease and Movement Disorders Unit, Neurology Service, IDIBAPS, CIBERNED, Hospital Clinic, Barcelona, Catalonia, Spain.
authors.forename: Yaroslau
authors.initials: Y
authors.lastname: Compta
authors.affiliation: The Queen Square Brain Bank for Neurological Disorders, Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom.
authors.forename: Tamas
authors.initials: T
authors.lastname: Revesz
authors.affiliation: Institute of Neuroscience, Newcastle University, Newcastle, United Kingdom.
authors.forename: David J
authors.initials: DJ
authors.lastname: Burn
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000187:drug effects*; D001058:Apomorphine / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018491:Dopamine Agonists / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D018491:Dopamine Agonists; D001058:Apomorphine
keywords: Parkinson's disease; amyloid; apomorphine; dementia