Downregulation of StAR driven neurosteroid biosynthesis as a distinctive feature in the brains of Alzheimer's disease patients.

•The steroidogenic acute regulatory (StAR) protein mediates neurosteroidogenesis that progressively deteriorates during human senescence.•We observed that postmortem brains of Alzheimer's disease (AD) patients exhibit suppression of StAR, free cholesterol (FC), and pregnenolone levels.•Attenuation of the steroidogenic response in AD brains was inversely correlated with Aβ and pTau accumulation.•Our findings demonstrate that downregulation of StAR governed neurosteroidogenesis correlated with aggregation of APP/Aβ and pTau in AD.