Familial Alzheimer's disease (FAD) tends to present with more prominent neurological symptoms including cerebellar signs than sporadic Alzheimer's disease (SAD). In order to elucidate the pathological differences in the cerebellum, which may be associated with the cerebellar symptoms, we have investigated morphometrically beta-amyloid deposits, atrocytosis, Purkinje cells and dentate neurons in the cerebellum of 10 FAD patients including two cases with the beta-amyloid precursor protein (APP) gene mutation (APP717 Val-->Ile), 10 SAD patients and 10 non-demented age-matched controls. The regions examined included the molecular, Purkinje cell and granular cell layers, the cerebellar white matter and the dentate nucleus. Purkinje cell density in FAD was significantly lower than in SAD. There were no significant differences in the density of dentate neurons among the three groups. The density of astrocytes in FAD was significantly greater than that in SAD in the granular cell and Purkinje cell layers and in the white matter. There were no significant differences in the amount and subtypes of beta-amyloid deposits (extracellular, vascular and perivascular) between FAD and SAD in all the regions investigated. In two cases with the APP mutation, both Purkinje cell loss and beta-amyloid deposition in the cerebellum were greater than the mean for FAD and SAD cases. Astrocytosis in the mutation cases was not greater than the mean for FAD cases except for the dentate nucleus in one case. Extracellular beta-amyloid deposits were not seen in any of the control cases although amyloid angiopathy was observed in one case. This study demonstrates for the first time that Purkinje cell loss and reactive astrocytosis of the cerebellum in FAD are more severe than in SAD, but that beta-amyloid deposition in the cerebellum in both FAD and SAD are similar. The more prominent neurological signs observed in FAD may be explained by more severe neurodegeneration than are found in sporadic cases.