Numerous studies indicate that aberrant amyloid precursor protein meta
bolism, elevated peroxidative damage, depressed energy metabolism and
altered calcium homeostasis are four pivotal deleterious factors in th
e pathogenesis of Alzheimer's disease. Cumulative evidence further sug
gests that these four factors are intimately interrelated, forming a d
eleterious network. Based on this new concept of 'deleterious network'
, a unifying hypothesis - the deleterious network hypothesis of Alzhei
mer's disease - is proposed. The main ideas of the hypothesis are deli
neated as follows: increases in free radical damage, alterations in am
yloid precursor protein metabolism, impairment of energy metabolism an
d abnormalities of calcium homeostasis are four cornerstones of a dele
terious network. Various risk factors of Alzheimer's disease can trigg
er the network by promoting the occurrence of one of these key compone
nts, resulting in the biological abnormalities of Alzheimer's disease.
Based on this new theory, a majority of the important observations ab
out Alzheimer's disease can be explained consistently and succinctly.