| Abstract: | The purposes of the study are to elucidate the ultimate stage of aging of the limbic system with observations of centenarian brains compared with dementia of the Alzheimer type (DAT), and to search for genetic factors that may influence formations of the senile changes in the limbic system. Neocortical as well as limbic regions of the brains from 13 centenarians were studied with younger control groups (average age about 80 years), that is 20 nondemented (ND) individuals and 20 patients with DAT. No centenarian subjects were clinically diagnosed as having DAT or satisfied neuropathological criteria for DAT. The densities of senile plaques (SP) in the centenarian brains tended to be higher than the ND subjects, but significantly lower than the DAT patients. The densities of neurofibrillary tangles (NFT) in the hippocampal region were significantly higher in the centenarians compared with the ND subjects. Five centenarian brains had an especially large number of NFT in the hippocampal region, which were comparable with DAT; however, NFT in the neocortical areas of the centenarians were scarce in contrast with DAT. The results suggest that DAT would not be an accelerated condition of the aging process represented by the centenarian brains, but a disease caused by a different pathological process. Further, a study was conducted to determine whether the polymorphisms of the apolipoprotein E (ApoE) and presenilin-1 (PS-1) genes were associated with SP and NFT in the limbic and neocortical areas of the brains from the 122 autopsy cases, including 36 DAT patients and 86 ND subjects. ApoEε4 allele frequency was significantly higher in the DAT patients (22.2%) compared with the ND subjects (7.6%) (P= 0.001), and individuals with the ε4 allele had higher densities of SP and NFT in the hippocampus. Further, ND elderly subjects without senile changes in the neocortical as well as limbic areas showed a significantly lower frequency of the ε4 allele and a significantly higher frequency of the ε2 allele compared with the other subjects. The PS-1 polymorphism was not associated with DAT, SP or NFT. The genetic polymorphisms of the other molecules may also contribute to expression of the age-related changes of the limbic system. |
