Ali Namvaran Abbas-Abad
1,2 
, Nayer Seyfizadeh
1, Mohammad Farzipour
1, Amir Pasokh
1,3, Sara Salatin
1, Neda Yazdanfar
4* 1 Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
2 Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha- NE, USA
3 Department of Pharmaceutical Sciences, Division of Pharmacology and Toxicology, University of Vienna, Vienna, Austria
4 Neuroscience Lab, Golestan Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Abstract
Alzheimer’s disease (AD) is a debilitating mental disorder that causes a gradual decline in cognitive function and memory loss. The disease is associated with the accumulation of amyloid beta (Aβ) peptide-containing plaques outside the cells and the formation of neurofibrillary tangles (NFTs) inside the neurons due to tau protein hyperphosphorylation. AD is considered a hypometabolic disease at the cellular level, characterized by decreased adenosine triphosphate (ATP) levels and elevated reactive oxygen species (ROS) levels. Mitochondria, the cellular powerhouse, provide energy for cellular metabolism and protect cells against excessive oxidative stress. During disease progression, toxic Aβ causes significant disruptions in mitochondria bioenergetics, proteolytic systems, electron transport chains, mitophagy, and mitochondria DNA (mtDNA), leading to an accumulation of damaged organelles. This results in a disruption of the cellular energy demands, ROS scavenging pathways, and autophagy. The compromised mitochondria function caused by toxic Aβ exacerbates the development and progression of AD. This review aimed to provide current insights into the interactions between mitochondria and Aβ in AD pathogenesis, highlighting the pivotal role of mitochondrial dysfunction in the disease’s progression.