Cortical alpha-synuclein load is associated with amyloid-beta plaque burden in a subset of Parkinson's disease patients.
Amyloid-beta (Abeta) peptide pathology in Alzheimer's disease (AD) comprises extracellular plaques and cerebral amyloid angiopathy (CAA). In Parkinson's disease (PD), alpha-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 Abeta may also promote alpha-synuclein fibrillization, we assessed the relationship between LB pathology and Abeta deposition in 40 cases of PD and 20 age-matched controls. In five cortical areas, we established the severity of Abeta 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 Abeta 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 Abeta plaque load. The APOE epsilon4 allele is over-represented in this subgroup. Our data indicate a strong association between pathologically identifiable Abeta plaque burden and alpha-synuclein load in cerebral cortex and provide indirect evidence that Abeta pathology is likely to be an important factor contributing to cognitive decline in a subgroup of PD patients.
Lashley
Tammaryn
T
Queen Square Brain Bank for Neurological Disorders, Department of Molecular Neuroscience, UCL Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
Holton
Janice L
JL
Gray
Emma
E
Kirkham
Konrad
K
O'Sullivan
Sean S
SS
Hilbig
Arlete
A
Wood
Nicholas W
NW
Lees
Andrew J
AJ
Revesz
Tamas
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D016631:Lewy Bodies / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000145:classification / Q000378:metabolism / Q000473:pathology; D058225:Plaque, Amyloid / Q000473:pathology*; D018709:Statistics, Nonparametric; D051844:alpha-Synuclein / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D051844:alpha-Synuclein