An immunohistochemical study of centenarian brains: a comparison.

To evaluate the pathology of centenarian brains, which would reflect the ultimate stage of the aging process, 13 centenarians (M:F=1:12; mean+/-SD, 101.5+/-1.5 years) from the consecutive autopsy series were studied. None had severe dementia compatible with Alzheimer's disease (AD). As younger controls, 20 nondemented (ND) individuals (79.8+/-3.2 years) and 20 AD patients (80.8+/-3.0 years) were selected. In addition to the routine examination including methenamine-Bodian staining, an immunohistochemical study was performed, using antibodies to amyloid beta protein, tau, ubiquitin, glial fibrillary acidic protein (GFAP), synaptophysin, and Ki-MIP (a marker of the microglial and perivascular cells). No centenarian subjects satisfied the neuropathological criteria for definite AD. The densities of senile plaques and neurofibrillary tangles (NFTs) were significantly lower in almost all examined subdivisions than the AD patients, and tended to be higher than the ND subjects. Cerebral amyloid angiopathy of the centenarian was less severe than the AD patients, as well as the proliterations of GFAP-positive astrocytes and Ki-MIP-positive microglial cells, and the loss of synaptic terminal density. The relative mildness of the age-related morphological changes in the centenarians compared with the AD patients supports the idea that AD would not be the ultimate condition of the aging process, but would develop through the switching to the pathological process.