The significance of Lewy bodies (LB) in the brains of patients with dementia is still poorly understood. In 1997, it was determined that LB are composed primarily of alpha-synuclein (AS), an abundant, soluble, pre-synaptic protein of unknown function. In 2000, we reported that LB could be detected with AS immunohistochemistry (IHC) in 60% of 145 sporadic Alzheimer’s Disease (AD) cases from the University of Pittsburgh’s AD Research Center (ADRC) cohort. LB were most commonly detected in the amygdala and were always most numerous in that area. Other investigators have shown similar results in early onset familial AD cases and Down's syndrome patients with AD. More recently, in order to evaluate the relationship between apolipoprotein E (ApoE) genotype and LBs in sporadic AD, we examined 121 sporadic AD cases. All 121 cases were evaluated by the University of Pittsburgh ADRC and fulfilled clinical and neuropathological criteria for a diagnosis of AD. The control group for ApoE4 allele frequency in the non-demented population consisted of 210 subjects clinically evaluated as non-demented by the ADRC. AS IHC detected LB in 74/121 (61.2%) of sporadic AD cases (AD+LB). The extent of LB formation in AD+LB cases ranged from those with numerous neocortical and nigral LB, to cases with LB only in the amygdala. The severity of LB formation was evaluated using a semi-quantitative scoring based on the international dementia with LB consensus criteria. A score of 10 (AD+LB10) indicates widespread neocortical LB formation and was found in 21 cases, while 53 cases of AD+LB had LB scores of less than 10 (AD+LB<10). There were 47 pure AD without LBs (38.9%). The ApoE4 allele frequency was 13.6% in controls, 36.2% in pure AD and 46.6% in AD+LB. However, in AD+LB10 cases, the ApoE4 allele frequency was increased to 52.4%. The frequency of ApoE4 carriers was 25% in controls, 64% in AD, 76% in AD+LB and 86% in AD+LB10 groups. Homozygosity for ApoE4 was found in 4/47 (9%) AD cases and in 4/21 (19%) AD+LB10 cases. ApoE4 odds ratio (95% confidence interval) for pure AD versus control was 5.1 (2.6-9.9) and for AD+LB10, 17.3 (4.9-61.2, p<0.0001 for both). These findings suggest that the ApoE4 allele is associated with LB formation in AD.
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