Alzheimer, mitochondria and gender

• Mitochondrial dysfunction is a common feature in aging and Alzheimer’s disease (AD).
• Changes in brain redox status may be linked to the loss of sex hormones in aging.
• Women have higher risk to develop AD than men.
• Sex hormones are neuroprotective against amyloid-β and abnormal tau toxicity.
• Protective effect of sex hormones may be linked to their bearing on bioenergetics.

Epidemiological studies revealed that two-thirds of Alzheimer’s disease (AD) patients are women and the drop of sex steroid hormones after the menopause has been proposed to be one risk factor in AD. Similarly, the decrease of circulating testosterone levels with aging may also increase the risk of AD in men. Studies attest the neuroprotective effects of sex hormones in animal models of AD, but clinical trial data remain controversial. Here, we discuss the implication of mitochondria in gender differences observed in AD patients and animal models of AD. We summarize the role of mitochondria in aging and AD, pointing to the potential correlation between the loss of sex hormones and changes in the brain redox status. We discuss the protective effects of the sex hormones, estradiol, progesterone and testosterone with a specific focus on mitochondrial dysfunction in AD. The understanding of pathological processes linking the loss of sex hormones with mitochondrial dysfunction and mechanisms that initiate the disease onset may open new avenues for the development of gender-specific therapeutic approaches.