Approximately 60% of familial and sporadic Alzheimer's disease (AD) cases manifest Lewy bodies (LBs), of which a major component is alpha-synuclein. Although the pathogenic role of alpha-synuclein in AD remains unclear, LB formation might be associated with pathological beta-amyloid (Abeta) overproduction. Here, we present the clinical and pathological characteristics of two affected family members from a pedigree with the E184D mutation of presenilin-1. One case presented with typical clinical features of AD, but the other case also developed clinical characteristics of dementia with Lewy bodies (DLB), including visual hallucinations, delusions, and parkinsonism. In both cases, neuropathological examination revealed numerous neurofibrillary tangles and severe Abeta deposition in senile plaques and amyloid angiopathy, in which Abeta42 rather than Abeta40 was predominant. Furthermore, remarkable alpha-synuclein pathology, including LBs and the accumulation of the non-Abeta component of AD amyloid (NAC) in plaques and astrocytes, was detected only in the case that presented with the symptoms of DLB. These findings suggest that (1) LB pathology can influence the clinical features of familial AD, (2) the E184D mutation of presenilin-1 may be associated with the LB formation through Abeta overproduction, although the process of LB formation is strongly affected by other unknown mechanisms, (3) in neurodegenerative disorders with LBs, there is a common pathophysiological background inducing NAC accumulation in neuritic plaques and astrocytes, and (4) the NAC accumulation in neuritic plaques is modulated by the abnormally aggregated tau protein.