The role of the phosphoinositide signalling system in the pathogenesis of sporadic Alzheimer's disease: a hypothesis.

Great advances have been made in recent years in our knowledge of the genetic mutations found in early onset familial Alzheimer's disease (AD) and their pathological consequences. The pathogenesis of sporadic AD, on the other hand, is less clear, although a central role of oxidative stress is indicated. In the AD brain, severe dysfunctions in the phosphoinositide signalling pathway have been reported. In view of the fact that (a) oxidative stress can adversely affect phosphoinositide breakdown and hence diacylglycerol-mediated activation of protein kinase C and (b) protein kinase C activation reduces the production of beta-amyloid peptide from amyloid precursor protein, it is possible that this represents a pathogenic pathway whereby oxidative stress can lead to amyloid deposition and the development of the disease.