[Neuronal death and neurotrophic factors in Alzheimer's disease]

Progressive neuronal death in cerebral cortex and subcortical regions may lead to dementia in Alzheimer's disease (AD). The neuronal death is accompanied by accumulation of senile plaques, neurofibrillary tangles and curly fibers. Recent immunocytochemical studies have suggested that abnormal sprouting responses, occurring in AD brain, may be involved in the formation of these lesions. The hypothesis concerning the lack of neurotrophic factors cannot explain abnormal sprouting responses in AD brain. We have investigated the mechanism of abnormal sprouting responses in AD brain, using primary culture of rat cerebral cortical neurons. In AD brain, loss of growth-inhibitory factors led to an apparently higher level of neurotrophic activity. One of the growth-inhibitory factors in normal aged brain was a 5 kDa heat-stable acidic protein. These results suggest that loss of inhibitory factors may induce abnormal sprouting responses in AD brain. In consequence, neurons might be exhausted and die.