查看文章

We recently reported1 that the glutamine (CAG) repeat polymorphism of exon 1 of the androgen receptor was associated with Alzheimer’s disease in men from the Oxford region. If this androgen receptor polymorphism indeed affects Alzheimer’s disease risk rather than being in linkage disequilibrium with the true risk factor, then we should see the effect through androgen receptor actions. The association should, for instance, be influenced by ligands of the androgen receptor. Androgen receptor isoforms are the main, perhaps sole, receptors for the principal mammalian androgens, testosterone and 5adihydrotestosterone. On binding ligand, the receptor moves from the cytoplasm to specific compartments of the nucleus (‘‘nuclear foci’’), where it interacts with coactivators and corepressors in the cell specific regulation of numerous genes. We therefore looked for an interaction in Alzheimer’s disease risk of the …