Age-dependent accumulation of advanced glycosylation end products in human neurons.

Glucose can react nonenzymatically with free amino groups on proteins and form advanced glycosylation end-products (AGEPs), that have been previously isolated and characterised in aging human connective tissues. In this study, we used immunocytochemistry to examine the distribution of AGEPs in the aging human brain. Our findings show that the pyramidal neurons selectively accumulate AGEP-containing vesicles in an age-dependent manner. In addition, our results demonstrate that AGEPs accumulate in the same type of neuron that degenerates in Alzheimer's disease.

Quantitative immunohistochemical analysis of the distribution of neurofibrillary tangles and senile plaques in the cerebral cortex of nonagenarians and centenarians.

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.

Dementia in the oldest-old: quantitative analysis of 12 cases from a psychiatric hospital.

To examine the neuropathological characteristics of senile dementia of the Alzheimer type (SDAT) in very old people, we performed a quantitative analysis of the distribution of neurofibrillary tangles and senile plaques in the brains of 12 demented patients aged from 96 of 104 years. The hippocampal formation and the inferior temporal cortex displayed numerous neurofibrillary tangles in most cases, whereas the superior frontal cortex was relatively spared. The only statistically significant difference between demented and control cases was in the density of neurofibrillary tangles in the CA1 field of the hippocampus. High senile plaque densities were observed in the cerebral cortex and were correlated with the duration of SDAT. These results confirm the crucial role of the hippocampus in the neuropathological diagnosis of SDAT in oldest-old patients. Furthermore, they suggest that senile plaque formation may be a pathological hallmark of severe SDAT in this particular age group.