Risk Factors and Mechanisms of Alzheimer's Disease Pathogenesis: Obviously and Obviously Not.

In their article, Chen and Fernandez (3) present a viewpoint in which they briefly consider the roles of the aging process, and risk factors associated with age-related degenerative diseases, in the pathogenesis of Alzheimer’s disease (AD). The authors forward both the general perspective, and a specific mechanism which they suggest underlies most cases of AD. They propose that 1) “several known risk factors most likely play a critical role in the late-onset sporadic AD”, and 2) “plaques and tangles occur spontaneously during aging as a result of a natural decline of energy metabolism and Ca signaling.” My responses to these two major conclusions are that 1) obviously, genetic and environmental risk factors play important roles in the pathogenesis of AD, and this is certainly not a new perspective; and 2) the proposal that a decline in energy metabolism and Ca signaling is central to the pathogenesis of AD is obviously not correct. In the following paragraphs I will elaborate on these two points. It is obviously the case that there are several important risk factors that increase the probability of developing AD. The aging process is the strongest risk factor for AD, and the molecular and cellular changes that occur in the brain dur-