Assessment of Mitochondrial Network Remodeling and Colocalization with Lysosomes in Primary Astrocyte Cultures from 5xFAD Mice

Mitochondrial dysfunction plays a crucial role in the pathogenesis of neurodegeneration and neurological disorders. It is a key factor in the development of Alzheimer’s disease, contributing to neuronal energy deficits, oxidative stress, and disruption of calcium homeostasis. Astrocytes are known to play an important role in maintaining neuronal health, including through the regulation of mitochondrial dynamics. However, changes occurring within the mitochondrial network of astrocytes themselves at early stages of pathology remain poorly understood. In the present study, we analyzed intracellular mitochondrial dynamics and mitophagy in astrocytes modeling Alzheimer’s disease. Our results demonstrate that astrocytes expressing pathological variants of PSEN and APP exhibit significant disruption of the mitochondrial network and reduced mitophagy activity at all stages of culturing compared to controls.