Amyloid-beta precursor protein expression and modulation in human embryonic stem cells: a novel role for human chorionic gonadotropin

The amyloid-β precursor protein (AβPP) is a ubiquitously expressed adhesion and neuritogenic protein whose processing has previously been shown to be regulated by reproductive hormones including the gonadotropin luteinizing hormone (LH) in human neuroblastoma cells. We report for the first time the expression of AβPP in human embryonic stem (hES) cells at the mRNA and protein levels. Using N- and C-terminal antibodies against AβPP, we detected both the mature and immature forms of AβPP as well as truncated variants (∼53 kDa, 47 kDa, and 29 kDa) by immunoblot analyses. Expression of AβPP is regulated by both the stemness of the cells and pregnancy-associated hormones. Addition of human chorionic gonadotropin, the fetal equivalent of LH that is dramatically elevated during pregnancy, markedly increased the expression of all AβPP forms. These results indicate a critical molecular signaling link between the hormonal environment of pregnancy and the expression of AβPP in hES cells that is suggestive of an important function for this protein during early human embryogenesis prior to the formation of neural precursor cells.