CELLULAR VULNERABILITY IN BRAIN AGING AND ALZHEIMERS-DISEASE - CLINICAL CORRELATES AND MOLECULAR BACKGROUND

The neuropathological changes associated with normal brain aging and A lzheimer's disease involve specific cortical circuits. Extensive hippo campal alterations are correlated with age-associated memory impairmen t, while substantial neurofibriliary tangle formation in neocortical a ssociation areas of the temporal lobe is a prerequisite for the develo pment of Alzheimer's disease. Several lines of evidence indicate that there is no correlation between senile plaque densities and the degree of dementia in this disorder. The cortical involvement in the ninth a nd tenth decades of life is different from that observed in younger pa tients in that parietal and cingulate areas are affected early in the course of Alzheimer's disease, and neocortical senile plaques densitie s are strongly correlated with the severity of dementia. Moreover, Alz heimer's disease pathology is characterized in these very old patients by high neurofibrillary tangle densities in the anterior CA1 field, b ut not in the entorhinal cortex and inferior temporal cortex. These pa tterns of lesion distribution are discussed in respect to the neuroche mical, genetic and metabolic factors which may influence the neuronal vulnerability in Alzheimer's disease.