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Effect of Estradiol on Neuronal Swedish-Mutated β-Amyloid Precursor Protein Metabolism: Reversal by Astrocytic Cells

2000; Elsevier BV; Volume: 271; Issue: 1 Linguagem: Inglês

10.1006/bbrc.2000.2581

1090-2104

Bruno Vincent, Jonathan D. Smith,

Amyloidosis: Diagnosis, Treatment, Outcomes

Alzheimer's disease is the most frequent neurodegenerative disorder in the aged population and is characterized by the deposition of the 40/42-residue amyloid β protein (Aβ), a proteolytic fragment of the β-amyloid precursor protein (APP). Recently, it has been shown that physiological doses of estradiol reduce the generation of endogenous Aβ in primary cortical neurons. Here we investigate the influence of estrogen in amyloidogenesis and sAPPα secretion in the CNS. By means of primary cortical neurons overexpressing humanized APP695 bearing the Swedish mutation (hAPP695sw), we analyzed APP maturation in the absence or in the presence of estrogen. We show that estrogen at a 2 μM concentration increases the release of the neuroprotective sAPPα fragment but does not reduce the release of Aβ in primary neurons overexpressing the Swedish-mutated form of APP. Furthermore, neurons cocultured with astrocytic cells or grown with astrocytes conditioned media do not exhibit the estrogen-induced increase in sAPPα secretion. Altogether, our data indicate that astrocytes interfere with estrogen in the regulation of sAPPα secretion, probably via secreted factor(s).