Hallmarks of AD, progression of the disease and mitochondrial dysfunction. A: The diagram shows the hallmarks in AD. B: The multiple pathogenic mechanisms contributing to the pathological hallmarks of AD consist of increased of ROS production, Aβ-induced mitochondrial dysfunction, and apoptosis due to impairment of mitochondrial Ca2+ handling ability, altered Ca2+ homeostasis, increased mitochondrial permeability transition pore opening, and promotion of cytochrome c release. Aβ inhibits protein import inside the mitochondria. APP also alters Ca2+ homeostasis leading to apoptosis. Mitochondrial DNA mutations and mitochondrial DNA damage are also involved in the pathogenesis of AD, and are associated with synaptic and neuronal loss, amyloid plaques, and NFTs. Perturbed cerebral energy metabolism plays a central role in multiple pathogenic cascades of AD. Abbreviations: AD, Alzheimer’s disease; Ca2+, calcium; Mptp, mitochondrial permeability transition pore; ROS, reactive oxygen species.