Mechanisms of neuronal death in Alzheimer's disease

Brain Pathology
Carl W Cotman, J H Su

Abstract

Recent data in cell culture has shown that brain neurons are particularly vulnerable to degeneration by apoptosis. Further the inducers that activate the program (e.g. beta-amyloid, oxidatative damage, low energy metabolism) correspond to conditions present in the Alzheimer's disease (AD) brain. This suggests the possibility that apoptosis may be one of the mechanisms contributing to neuronal loss in this disease. Indeed, some neurons in vulnerable regions of the AD brain show evidence of DNA damage, nuclear apoptotic bodies, chromatin condensation, and the induction of select genes characteristic of apoptosis in cell culture and animal models. This suggests the existence of apoptosis in the AD brain, a hypothesis also consistent with evolving research in one of the regulatory functions of the presenilin genes. On the other hand, DNA damage is present in the majority of neurons in vulnerable regions in early and mild cases. In most tissues, cells in fully activated apoptosis degenerate and are removed within hours to days and thus it seems all DNA damage is unlikely to signify terminal apoptosis. The presence of extensive DNA damage suggests an acceleration of damage, faulty repair process, loss of protective mechanisms, or an ...Continue Reading

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