Estrogen reduces neuronal generation of Alzheimer β-amyloid peptides

Alzheimer's disease (AD) is characterized by the accumulation of cerebral plaques composed of 40- and 42-amino acid beta-amyloid (A beta) peptides, and autosomal dominant forms of AD appear to cause disease by promoting brain A beta accumulation. Recent studies indicate that postmenopausal estrogen replacement therapy may prevent or delay the onset of AD. Here we present evidence that physiological levels of 17 beta-estradiol reduce the generation of A beta by neuroblastoma cells and by primary cultures of rat, mouse and human embryonic cerebrocortical neurons. These results suggest a mechanism by which estrogen replacement therapy can delay or prevent AD.