PS2 protein expression is upregulated by sex steroids in the cerebral cortex of aging mice

Mutations in presenilin (PS) genes cause majority of early onset Alzheimer's disease (AD), an age related neurodegenerative disorder. PS proteins undergo proteolytic cleavage to produce biologically active fragments, which constitute the catalytic core of the gamma-secretase enzyme. This enzyme cleaves beta-amyloid precursor protein (betaAPP) to generate Abeta peptides, which are influenced by sex steroids. Recently we have reported the downregulation of PS1 expression by sex steroids in the brain of adult mice. Here we have examined the effect of gonadectomy and subsequent administration of gonadal hormones 17beta-estradiol and testosterone on the level of PS2 C-terminal fragment (CTF) in the cerebral cortex of adult and old AKR strain mice of both sexes. PS2 expression was downregulated following gonadectomy, but upregulated by supplementation of gonadal steroids in both age groups and sexes. Thus these results demonstrate up-regulation of PS2 protein expression by sex steroids, which in turn may influence PS2 associated brain functions.