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 Lashley
  • Janice L. Holton
  • Emma Gray
  • Konrad Kirkham
  • Sean S. O’Sullivan
  • Arlete Hilbig
  • Nicholas W. Wood
  • Andrew J. Lees
  • Tamas Revesz
Original Paper

DOI: 10.1007/s00401-007-0336-0

Cite this article as:
Lashley, T., Holton, J.L., Gray, E. et al. Acta Neuropathol (2008) 115: 417. doi:10.1007/s00401-007-0336-0

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.

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Tammaryn Lashley
    • 1
  • Janice L. Holton
    • 1
  • Emma Gray
    • 1
  • Konrad Kirkham
    • 1
  • Sean S. O’Sullivan
    • 2
  • Arlete Hilbig
    • 1
  • Nicholas W. Wood
    • 3
  • Andrew J. Lees
    • 1
    • 2
  • Tamas Revesz
    • 1
  1. 1.Queen Square Brain Bank for Neurological Disorders, Department of Molecular Neuroscience, UCL Institute of NeurologyUniversity College LondonLondonUK
  2. 2.Reta Lila Weston Institute of Neurological Studies, Department of Molecular Neuroscience, UCL Institute of NeurologyUniversity College LondonLondonUK
  3. 3.Neurogenetics, Department of Molecular Neuroscience, UCL Institute of NeurologyUniversity College LondonLondonUK