DELETERIOUS NETWORK HYPOTHESIS OF ALZHEIMERS-DISEASE

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.