Dehydroepiandrosterone (DHEA) increases production and release of Alzheimer's amyloid precursor protein

• Published in: Life sciences (1973) 1996, Vol.59 (19), p.1651-1657
• Main Authors: Danenberg, H.D., Haring, R., Fisher, A., Pittel, Z., Gurwitz, D., Heldman, E.
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - metabolism; Alzheimer's disease; Amyloid beta-Protein Precursor - biosynthesis; Amyloid beta-Protein Precursor - metabolism; amyloid precursor protein; Animals; Cell Count; dehydroepiandrosterone; Dehydroepiandrosterone - pharmacology; Dose-Response Relationship, Drug; Enzyme Inhibitors - pharmacology; Humans; Indoles - pharmacology; Maleimides - pharmacology; PC12 Cells; Protein Biosynthesis; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - metabolism; Rats; Signal Transduction
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/0024-3205(96)00496-1

Dehydroepiandrosterone (DHEA), the major secretory product of the human adrenal cortex, significantly declines with advanced age. We have previously demonstrated that DHEA prevents the reduction in non-amyloidogenic APP processing, following prolonged stimulation of the muscarinic receptor, in PC12 cells that express the ml acetylcholine-receptor. The present study examined whether this effect may be mediated via modulation of APP metabolism. It was found that DHEA treatment increases the content of membrane-associated APP holoprotein by 24%, and the accumulation 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 synthesis and secretion. We propose that the age-associated decline in DHEA levels may be related to the pathological APP metabolism observed in Alzheimer's disease.