Alzheimer's disease (AD) represents a heterogeneous disorder, and several factors have been associated with its development. The presence of the apolipoprotein E type (APOE) epsilon 4 allele has been proposed as a risk factor for AD, but how it influences the development of the characteristic hallmarks of the disease remains unknown. In the present study, the neuropathological changes and levels of both core PHF-tau and normal tau protein in 4 neocortical areas, cerebellum and medial temporal cortex were determined in 18 AD cases. The extent of these changes was compared between 10 cases possessing an epsilon 4 allele and 8 cases without. These two groups were indistinguishable in terms of neurofibrillary pathology, whereas cases with an epsilon 4 allele had more diffuse plaques, particularly in the temporal neocortex. Biochemically, there was no difference in the levels of PHF-tau protein between the two groups. These data indicate that APOE epsilon 4 allele may influence deposition of diffuse amyloid, but altered tau protein processing, which underlies the development of the neurofibrillary pathology in AD, is not influenced by this allele.