Dementia with Lewy bodies: What is its relationship to Alzheimer's disease?

The relationship between dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) is poorly understood. In this chapter, the issue is discussed from a clinical and histopathological perspective, with an emphasis on early-onset familial forms of AD (FAD) related to identifiable genetic abnormalities. FAD cases frequently have Lewy bodies in the amygdala, and more widespread Lewy body formation is common. Overall, AD cases resulting from point mutations are more likely to develop Lewy bodies than cases with Down's syndrome. However, no specific point mutations of the amyloid precursor protein (APP) and presenilin-1 (PS-1) genes are consistently associated with Lewy body formation. FAD subjects with Lewy bodies inconsistently meet clinical consensus criteria for possible or probable DLB. Symptoms of DLB are more likely to be present when Lewy bodies occur in large numbers in multiple regions. However, some symptoms of DLB, such as spontaneous parkinsonism, occur in specific kindreds, including our C410Y PS-1 family. Here, parkinsonism occurs primarily in association with P-amyloid plaques and neuritic degeneration in the basal ganglia, rather than Lewy bodies. The frequent occurrence of Lewy bodies in early-onset FAD cases suggests that the genetic abnormalities leading to early-onset AD also may predispose individuals to developing Lewy bodies. Lewy body formation, particularly that which occurs in the amygdala, may be a manifestation of phenotypic heterogeneity seen in the AD process.