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.