To evaluate the pathology of centenarian brains, which would reflect t
he ultimate stage of the aging process, 13 centenarians (M:F=1:12; mea
n+/-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 ad
dition to the routine examination including methenamine-Bodian stainin
g, an immunohistochemical study was performed, using antibodies to amy
loid beta protein, tau, ubiquitin, glial fibrillary acidic protein(GFA
P),synaptophysin, and Ki-MIP (a marker of the microglial and perivascu
lar cells). No centenarian subjects satisfied the neuropathological cr
iteria for definite AD. The densities of senile plaques and neurofibri
llary tangles (NFTs) were significantly lower in almost all examined s
ubdivisions than the AD patients, and tended to be higher than the ND
subjects. Cerebral amyloid angiopathy of the centenarian was less seve
re than the AD patients, as well as the proliferations of GFAP-positiv
e astrocytes and Ki-MIP-positive microglial cells, and the loss of syn
aptic terminal density. The relative mildness of the age-related morph
ological changes in the centenarians compared with the AD patients sup
ports the idea that AD would not be the ultimate condition of the agin
g process, but would develop through the switching to the pathological
process. (C) 1998 Elsevier Science B.V.