Pathology of familial Alzheimer's disease with Lewy bodies

The neuropathological findings of three cases from two pedigrees with early onset familial Alzheimer's disease (FAD) are reported. Affected members of the first family, including cases 1 and 2 reported here, are known to have 717 valine to isoleucine mutation of the amyloid precursor protein (APP) gene, while the genetic background of the disease has not been clarified yet in the second family. In all three cases, in addition to the classical histological findings associated with Alzheimer's disease (AD), both nigral and cortical Lewy bodies (LBs) occurred. The association of LBs with AD type pathology, which may be observed in both sporadic and familial AD, raises important nosological issues. These include a possible overlap between AD and other neurodegenerative conditions presenting primarily with LBs. In this respect the clinically and neuropathologically distinct disease entity described under the terms of "senile dementia of the Lewy body type" and "Lewy body variant of AD" may be especially important. The occurrence of LBs in association with severe AD-type histological changes in sporadic and especially in some familial AD cases indicate that these inclusions may be another expression of the altered cytoskeleton in AD.