To investigate the neuropathological differences between normal aging and senile dementia of the Alzheimer type (SDAT) in very old people and to see how they compare with a younger population of demented elderly people, we performed an immunohistochemical quantitative analysis of the topography of senile plaques and neurofibrillary tangles in a series of 31 elderly patients aged from 96 to 102 years. According to the medical records, two groups were considered: 7 patients presenting with clinically documented SDAT and 24 patients with no or very mild cognitive impairment. The densities of senile plaques were comparable in both groups. Extensive neurofibrillary tangle formation was restricted to the CA1 hippocampal field of demented subjects, whereas the superior frontal cortex showed rare neurofibrillary tangles, independently of the clinical diagnosis. These results indicate an absence of direct correlation between the number of senile plaques and the clinical manifestation of SDAT. Furthermore, they suggest that the dementing process may involve different cortical structures in nonagenarians and centenarians than in younger demented individuals where a widespread cortical involvement is generally observed. Thus, the neurofibrillary tangle density in the CA1 field may be critical for the neuropathological diagnosis of SDAT in this particular group of very old patients.