Among the neurodegenerative diseases, Alzheimer's disease (AD) is a predominant public health issue, affecting 16 million people around the world. It is clinically manifested by the presence of amyloid plaques (Aβ) and neurofibrillary tangles (NFT) within the brain. Due to intraneuronal processing, Aβ interacts with cellular targets such as mitochondria, ER, and Golgi apparatus and hampers their normal functions. Alteration in the mitochondrial function, closely related to the production of reactive oxygen species (ROS), Ca+2 overload, and apoptosis in the brain, is one of the key pathological events studied in AD pathogenesis. It is also an important pivot for the intracellular interaction with ER and Golgi through signal transduction and membrane contact to regulate cell survival and death mechanism. Alteration in mitochondrial function is intimately connected with abnormal ER or Golgi function. Stimuli that enhance perturbation in the normal ER or Golgi organelles function can involve mitochondria mediated apoptotic cell death. In this review, we address the importance of the mitochondria and their cross talk with ER and Golgi in AD pathogenesis and animal models with a therapeutic strategy to improve the mitochondrial functions.