Amyloid Beta and Mitochondrial Perturbations: An Update on Mechanisms and Methods

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.