The androgen receptor CAG repeat and serum testosterone in the risk of Alzheimer’s disease in men

repeat and serum testosterone in the risk of Alzheimer’s disease in men We recently reported 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 androgen receptor CAG polymorphism with serum concentrations of total testosterone. We studied 207 elderly men, 79 with sporadic Alzheimer’s disease (mean (SD) onset age, 70 (9) years) and 128 controls (mean age, 75 (10) years), all from the cohort of the Oxford Project to Investigate Memory and Ageing (OPTIMA). Of the 79 Alzheimer cases, 45 were necropsy confirmed as having Alzheimer’s disease by CERAD criteria (40 ‘‘definite’’ and five ‘‘probable’’) and 34 were diagnosed as ‘‘probable Alzheimer’s disease’’ by NINCDS-ADRDA criteria. All 128 controls were without detectable cognitive dysfunction and with CAMCOG scores of more than 80. Serum concentrations of total testosterone and androgen receptor allele lengths were determined as previously described. 2 Testosterone concentrations were divided into tertiles (69 subjects in each tertile): the upper tertile was .19 nmol/l, the middle between 13 and 19 nmol/l, and the lower (13 nmol/l. Short androgen receptor alleles were (20 CAG repeats. Logistic regression analysis was by R.