Our key findings were that (1) APP/Aβ and mutant tau-overexpressing cells present distinct bioenergetic impairments, with APP/Aβ having the strongest deleterious effect on mitochondrial function and (2) the male steroid hormone, testosterone, was more efficient in alleviating mitochondrial deficits in a model of AD-related amyloidopathy, whereas the female steroid hormones, progesterone and estrogen, were more efficient in increasing bioenergetic outcomes in a model of AD-related tauopathies. Here, APP is linked to tauopathy.