Aberrant Protein Kinase C Cascades in Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is characterized by the dysfunction and eventual death of selected sets of central nervous system cortical neurons. This deterioration of neurons is responsible for the cognitive impairment of patients. The reason for this neuronal death is not known. In 1981, Appel proposed that the lack of a neurotrophic factor might be responsible for neuronal loss in AD. Two years later, Hefti suggested that NGF may be the neurotrophic factor missing in AD. However, normal levels of NGF mRNA have been found in AD brain (Goedert et al., 1986), indicating that a new hypothesis might be necessary to explain neuronal dysfunction and loss in AD. Indeed, we now know that many classes of neurons that are not responsive to NGF are also lost in AD. Furthermore, there is direct evidence for increased neurotrophic activity in AD brain (Uchida et al., 1988), suggesting that rather than a generalized deficit of trophic factors, a defect exists in the responsive machinery within the target cells.