Tau, amyloid, iron, oligodendrocytes ferroptosis, and inflammaging in the hippocampal formation of aged rats submitted to an aerobic exercise program.

Alzheimer's disease is a progressive neurodegenerative disease affecting memory, language, and thinking with no curative treatment. Symptoms appear gradually, and pathological brain changes may occur twenty years before the physical and psychological signs, pointing to the urgent development of preventive interventions. Physical activity has been investigated as a preventive tool to defeat the main biological features of AD: pathological amyloid protein plaques, tau tangles, myelin degeneration, and iron deposits in the brain. This work quantifies tau tangles, amyloid, iron, and ferroptosis in oligodendrocytes in the aged rat hippocampal formation and statistically correlates neuron-neuron, neuron-glia, and glia-glia crosstalk and the effect of physical exercise on it. Our results indicate that iron overload in the oligodendrocytes is an inducer of ferroptosis; physical exercise reduces inflammaging, and improves axon-myelin volume relations; tau, amyloid, iron, and hippocampal formation cells present statistical correlations. Our data suggest the beneficial effects of physical exercise in AD and a mathematical relationship between the hippocampal formation cells in sedentary and active individuals, which should be considered in human and animal studies as a guide to a better understanding of crosstalk physiology.