Deleterious network: a testable pathogenetic concept of Alzheimer's disease

Cumulative evidence has indicated that a deleterious network is formed on the basis of close interactions among abnormal amyloid precursor protein (APP) metabolism, oxidative damage, compromised energy metabolism and impaired calcium homeostasis. A unifying hypothesis-the deleterious network hypothesis of Alzheimer's disease (AD)-proposes that the deleterious network, not any single factor, is the common pathway of AD. Aging and multiple genetic or environmental factors could trigger the network by promoting the occurrence of one or more of the key detrimental factors, leading to a number of pathological changes of the disorder. This new hypothesis appears to unify some major theories of AD, providing a sound basis for consistent explanations to a large variety of the observations about the disorder. In this article upto-date delineation of the novel theory is given. Three types of studies are also proposed for further determining the validity of the new hypothesis. Based on this theory, it is suggested that combinative applications of the approaches which can reduce the incidence of the four key pathological factors could become a new therapeutic strategy of AD.