In this episode of The Physiological Reviews Podcast, Professor Giovanni Mann (King’s College London) interviews authors Prof. Marzia Perluigi (Sapienza University of Rome) and Prof. D. Allan Butterfield (University of Kentucky) about their recently published Review on the oxidative stress hypothesis of Alzheimer Disease. The authors provide a comprehensive overview of amyloid beta-peptide associated mechanisms, the use of redox proteomics to define roles of lipid and protein oxidation, and the antioxidant strategies utilized to modulate the progression of Alzheimer Disease (AD) in order to improve the quality of life for individuals with this severe disorder. Prof. Perluigi explains that because the brain is particularly susceptible to free radical damage, it is likely that lipid peroxidation is among the initiating toxic events in AD pathophysiology, with amyloid deposits reacting with membrane lipids that in turn target other cellular components such as proteins and nucleic acid. Listen as we discuss the role of astrocytes in the pathogenesis of AD, as well as the utility of animal models to plan preclinical trials and clarify molecular mechanisms involved in neuropathology of AD. Come for the discussion of the role that oxidative stress plays in the pathogenesis of AD, and stay for the illuminating conversation about the paths Prof. Butterfield and Prof. Perluigi have followed in pursuing their research training and careers in science with enthusiasm, dedication, and willingness to develop international research collaborations in the field of redox biology and chemistry associated with Alzheimer Disease.   Marzia Perluigi, Fabio Di Domenico, and D. Allan Butterfield Oxidative damage in neurodegeneration: roles in the pathogenesis and progression of Alzheimer disease Physiological Reviews, published July 19, 2023. DOI: 10.1152/physrev.00030.2022