DELETERIOUS NETWORK - A TESTABLE PATHOGENETIC CONCEPT OF ALZHEIMERS-DISEASE

Cumulative evidence has indicated that a deleterious network is formed on the basis of close interactions among abnormal amyloid precursor p rotein (APP) metabolism, oxidative damage, compromised energy metaboli sm and impaired calcium homeostasis. A unifying hypothesis - the delet erious network hypothesis of Alzheimer's disease (AD)- proposes that t he deleterious network, not any single factor, is the common pathway o f AD. Aging and multiple genetic or environmental factors could trigge r the network by promoting the occurrence of one or more of the key de trimental 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 var iety of the observations about the disorder. In this article up-to-dat e delineation of the novel theory is given. Three types of studies are also proposed for further determining the validity of the new hypothe sis. Based on this theory, it is suggested that combinative applicatio ns of the approaches which can reduce the incidence of the four key pa thological factors could become a new therapeutic strategy of AD.