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

Amyloid-beta (A beta) 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 A beta may also promote alpha-synuclein fibrillization, we assessed the relationship between LB pathology and A beta deposition in 40 cases of PD and 20 age-matched controls. In five cortical areas, we established the severity of A beta 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 A beta 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 A beta plaque load. The APOE epsilon 4 allele is over-represented in this subgroup. Our data indicate a strong association between pathologically identifiable A beta plaque burden and alpha-synuclein load in cerebral cortex and provide indirect evidence that A beta pathology is likely to be an important factor contributing to cognitive decline in a subgroup of PD patients.