Antibodies to alpha-synuclein (AS) now provide a sensitive and specific method for the detection of Lewy bodies (LBs) and their use will allow a more accurate determination of the prevalence of LBs in Alzheimer's Disease (AD). Studies using AS immunohistochemistry (IHC) have found LBs in the amygdala of over 60% early onset familial AD and in 50% of Down's syndrome patients with AD, however, no studies have reported the use of AS IHC to detect LBs in a large cohort of sporadic AD. This study examined 145 sporadic AD cases diagnosed using CERAD criteria from 1995-1999 for the presence of LBs using AS IHC. AS IHC detected LBs in 88/145 (60.7%) of sporadic AD cases. Similarly, LBs were found in 56.8% of the 95 cases fulfilling the more stringent NIA-RI criteria for the diagnosis of AD (Braak stage 5-6). In all cases with LBs, the amygdala was involved and LBs were always most numerous in this area, however, in some cases LBs in the substantia nigra were rare or not present. In conclusion, this study found that AS IHC detects LBs in the majority of sporadic AD cases and that the amygdala is the most commonly affected region.