Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by loss of function and eventual death of neurons in the brain. Multiple studies have highlighted the involvement of mitochondria in the initiation and advancement of neurodegenerative diseases. Mitochondria are essential for ATP generation, bioenergetics processes, the regulation of calcium homeostasis and free radical scavenging. Disrupting any of these processes has been acknowledged as a major contributor to the pathogenesis of common neurodegenerative diseases, especially AD. Several longitudinal studies have demonstrated type 2 diabetes (T2D) as a risk factor for the origin of dementia leading towards AD. Even though emerging research indicates that anti-diabetic intervention is a promising option for AD prevention and therapy, results from clinical trials with anti-diabetic agents have not been effective in AD. Interestingly, defective mitochondrial function has also been reported to contribute towards the onset of metabolic disorders including obesity and T2D. The most prevalent consequences of mitochondrial dysfunction include the generation of inflammatory molecules and reactive oxygen species (ROS), which promote the onset and development of metabolic impairment and neurodegenerative diseases. Current evidence indicates an association of impaired peripheral mitochondrial function with primary AD pathology; however, the mechanisms are still unknown. Therefore, in this review, we discuss if mitochondrial dysfunction-mediated metabolic disorders have a potential connection with AD development, then would addressing peripheral mitochondrial dysfunction have better therapeutic outcomes in preventing metabolic disorder-associated AD pathologies.
Keywords: Alzheimer’s disease; metabolic disorders; mitochondrial dysfunctions; neurodegeneration.