Original Paper

Acta Neuropathologica

, Volume 115, Issue 4, pp 417-425

Cortical α-synuclein load is associated with amyloid-β plaque burden in a subset of Parkinson’s disease patients

  • Tammaryn LashleyAffiliated withQueen Square Brain Bank for Neurological Disorders, Department of Molecular Neuroscience, UCL Institute of Neurology, University College London
  • , Janice L. HoltonAffiliated withQueen Square Brain Bank for Neurological Disorders, Department of Molecular Neuroscience, UCL Institute of Neurology, University College London
  • , Emma GrayAffiliated withQueen Square Brain Bank for Neurological Disorders, Department of Molecular Neuroscience, UCL Institute of Neurology, University College London
  • , Konrad KirkhamAffiliated withQueen Square Brain Bank for Neurological Disorders, Department of Molecular Neuroscience, UCL Institute of Neurology, University College London
  • , Sean S. O’SullivanAffiliated withReta Lila Weston Institute of Neurological Studies, Department of Molecular Neuroscience, UCL Institute of Neurology, University College London
  • , Arlete HilbigAffiliated withQueen Square Brain Bank for Neurological Disorders, Department of Molecular Neuroscience, UCL Institute of Neurology, University College London
  • , Nicholas W. WoodAffiliated withNeurogenetics, Department of Molecular Neuroscience, UCL Institute of Neurology, University College London
  • , Andrew J. LeesAffiliated withQueen Square Brain Bank for Neurological Disorders, Department of Molecular Neuroscience, UCL Institute of Neurology, University College LondonReta Lila Weston Institute of Neurological Studies, Department of Molecular Neuroscience, UCL Institute of Neurology, University College London
  • , Tamas ReveszAffiliated withQueen Square Brain Bank for Neurological Disorders, Department of Molecular Neuroscience, UCL Institute of Neurology, University College London Email author 

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Abstract

Amyloid-β (Aβ) peptide pathology in Alzheimer’s disease (AD) comprises extracellular plaques and cerebral amyloid angiopathy (CAA). In Parkinson’s disease (PD), α-synuclein forms intraneuronal Lewy bodies (LBs), and cortical LBs are thought to play a major role in cognitive decline designated as PD with dementia. As there is increasing evidence that Aβ may also promote α-synuclein fibrillization, we assessed the relationship between LB pathology and Aβ deposition in 40 cases of PD and 20 age-matched controls. In five cortical areas, we established the severity of Aβ plaque load using an approach similar to that recommended by CERAD in AD. LB densities were determined using a morphometric approach. CAA was graded using previously described scales. The APOE genotype was established in 38 PD and 19 control cases. We have found that the overall Aβ plaque burden and, in particular, the diffuse plaque load shows a statistically significant ‘large’ correlation with the overall cortical LB burden. The strength of this correlation further increases in PD cases (about 50% of the cases) with moderate to high Aβ plaque load. The APOE ε4 allele is over-represented in this subgroup. Our data indicate a strong association between pathologically identifiable Aβ plaque burden and α-synuclein load in cerebral cortex and provide indirect evidence that Aβ pathology is likely to be an important factor contributing to cognitive decline in a subgroup of PD patients.