Associations between gonadotropins, testosterone and β amyloid in men at risk of Alzheimer's disease

Testosterone and gonadotropins have been associated with cognitive decline in men and the modulation of beta amyloid (A beta) metabolism. The relatively few studies that have investigated whether changes in one or a combination of these hormones influence A beta levels have focused primarily on plasma A beta(1-40) and not on the more pathogenic A beta(1-42). Currently, no study has investigated whether these hormones are associated with an increase in brain amyloid deposition, ante mortem. Through the highly characterised Australian imaging, biomarkers and lifestyle study, we have determined the impact of these hormones on plasma A beta levels and brain amyloid burden (Pittsburgh compound B (PiB) retention). Spearman's rank correlation and linear regression analysis was carried out across the cohort and within subclassifications. Luteinizing hormone (LH) was the only variable shown, in the total cohort, to have a significant impact on plasma A beta(1-40) and A beta(1-42) levels (beta = 0.163, P<0.001; beta = 0.446, P<0.001). This held in subjective memory complainers (SMC) (A beta(1-40); beta = 0.208, P = 0.017; A beta(1-42); beta 0.215, P = 0.017) but was absent in mild cognitive impairment (MCI) and Alzheimer's disease (AD) groups. In SMC, increased frequency of the APOE-epsilon 4 allele (beta = 0.536, P<0.001) and increasing serum LH levels (beta = 0.421, P = 0.004) had a significant impact on PiB retention. Whereas in MCI, PiB retention was associated with increased APOE-epsilon 4 allele copy number (beta = 0.674, P<0.001) and decreasing calculated free testosterone (beta = -0.303, P = 0.043). These findings suggest a potential progressive involvement of LH and testosterone in the early preclinical stages of AD. Furthermore, these hormones should be considered while attempting to predict AD at these earliest stages of the disease.