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Multiple causes, multiple targets AD as an heterogeneous disease The amyloid hypothesis as the essential cause of neuronal loss and brain atrophy is a matter of discussion mainly because removal or reduction of amyloid plaques by immunological treatments display no significant effect on clinical symptoms of AD [39, 140]

doi: 10.1074/jbc.M307600200 81 ItoKIkedaSKojimaNMiuraMShimizu-SaitoKYamaguchiIet al

Cai LJ, Tu L, Huang XM, Huang J, Qiu N, Xie GH, et al

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In addition, mtDNA mutations are also associated with abnormal mitochondrial ETC separation, reduced energy supply, and increased ROS production, which has been validated in the treatment of cardiovascular diseases (25)