Alpha-synuclein-immunoreactive cortical Lewy bodies are associated with cognitive impairment in Parkinson's disease

Amygdala, hippocampus and six cortical gyri were examined for the Lewy body (LB) degeneration and Alzheimer's disease (AD) type changes in 45 patients with Parkinson's disease (PD). For detection of LBs, the brain areas were stained with an antibody against alpha-synuclein. The extent of neuropathol ogical lesions was investigated in relation to cognitive dysfunction and ap olipoprotein E (apoE) epsilon 4 allele dosage. At least one cortical LB was found in 95% of cases (43/45). Furthermore, 40% of cases (18/45) had histo logical findings of definite AD (CERAD class C). Those PD cases with the ap oE epsilon 4 allele had a significantly greater number of cortical LBs than those without the apoE epsilon 4 allele, but this was statistically signif icant only in precentral, angular and temporal gyri. The LB density correla ted better with the number of plaques than with the density of tangles. The number of LBs in several cortical areas correlated significantly with the cognitive impairment. In stepwise linear regression analysis, the number of LBs in the cingulate gyrus and the amount of tangles in the temporal corte x remained statistically significant. When the CERAD class C was excluded, the correlation between cognitive decline and the number of LBs in cortical areas became even more pronounced. A stepwise linear regression analysis i n these cases found the number of LBs in the frontal gyrus to be the statis tically most significant predictor of cognitive impairment. This study show s, for the first time, that in PD, alpha-synudein-positive cortical LBs are associated with cognitive impairment independent of AD-type pathology.