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.
        
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Danenberg HD, Haring R, Fisher A, Pittel Z, Gurwitz D, Heldman E (1996) Dehydroepiandrosterone (DHEA) increases production and release of Alzheimer's amyloid precursor protein Life Sciences59: 1651-7
Danenberg HD, Haring R, Fisher A, Pittel Z, Gurwitz D, Heldman E (1996) Life Sciences59: 1651-7