Purkinje cell loss and astrocytosis in the cerebellum in familial and sporadic Alzheimer's disease.

In order to elucidate further the pathological differences between familial Alzheimer's disease (FAD) and sporadic Alzheimer's disease (SAD), Purkinje cells and astrocytosis in the cerebellum of 10 FAD patients including two cases with the beta-amyloid precursor protein (APP) gene mutation in codon 717 (APP717 Val-->Ile), 10 SAD patients and 10 non-demented, age-matched controls were morphometrically investigated using immunohistochemistry. The regions examined included the molecular, Purkinje cell and granular cell layers, and the cerebellar white matter. This is the first report of a significantly decreased Purkinje cell density in FAD when compared to SAD. The density in SAD was also significantly decreased when compared to controls. In addition, the astrocyte density in FAD was significantly greater than that of SAD in the Purkinje cell layer, granular cell layer, and white matter. The density in SAD was also greater than that in controls, but not significantly in the granular cell layer and white matter. In the cases with the APP717 (Val-->Ile) mutation, Purkinje cell loss in the cerebellum was greater than the mean for FAD and SAD cases, while the astrocyte density was lower than the mean of all FAD cases, but higher than the mean of SAD cases. This study demonstrates that Purkinje cell loss and astrocytosis in FAD in the cerebellum are greater than in SAD, indicating that the cerebellum is more affected in FAD than in SAD.