DEHYDROEPIANDROSTERONE (DHEA) INCREASES PRODUCTION AND RELEASE OF ALZHEIMERS AMYLOID PRECURSOR PROTEIN

Dehydroepiandrosterone (DHEA), the major secretory product of the huma n adrenal cortex, significantly declines with advanced age. We have pr eviously demonstrated that DHEA prevents the reduction in non-amyloido genic APP processing, following prolonged stimulation of the muscarini c receptor, in PC12 cells that express the ml acetylcholine-receptor. The present study examined whether this effect may be mediated via mod ulation of APP metabolism. It was found that DHEA treatment increases the content of membrane-associated APP holoprotein by 24%, and the acc umulation of secreted APP in the medium by 63%. No increase in viable cell number nor in nonspecific protein production was observed in DHEA -treated cells. Thus, DHEA seems to increase specifically both APP syn thesis and secretion. We propose that the age-associated decline in DH EA levels may be related to the pathological APP metabolism observed i n Alzheimer's disease.