Aβ deposition is associated with enhanced cortical α-synuclein lesions in Lewy body diseases

In order to understand better the neuropathological substrate of dementia in Parkinson's disease (PD) and to examine its interactions with Alzheimer's disease (AD), we examined autopsy brains from 21 cases of PD and Lewy body disease (LBD) with dementia. We separated brains in two groups according to the presence of A beta deposits. In brains without Ap, we found few or no Lewy bodies (LB) in the cerebral cortex. By contrast, in brains with Ap, we observed significant increases in LB in the cerebral cortex (p < 0.01) and a-synuclein immunoreactive lesions in the cingulate cortex (p < 0.01). Immunoblots of a-synuclein from cingulate cortex in brains with A beta showed significantly higher levels of insoluble a-synuclein compared to brains without Ap. Our observations indicate that in cases of PD with dementia, the neocortex is not necessarily involved by LB. Furthermore, the presence of Ap deposits in the cerebral cortex was associated with extensive a-synuclein lesions and higher levels of insoluble a-synuclein. This suggests that A beta enhances the development of cortical a-synuclein lesions in cases of PD. (c) 2004 Elsevier Inc. All rights reserved.