Testosterone and gonadotropins have been associated with cognitive decline in men and the modulation of β amyloid (Aβ) metabolism. The relatively few studies that have investigated whether changes in one or a combination of these hormones influence Aβ levels have focused primarily on plasma Aβ1–40 and not on the more pathogenic Aβ1–42. 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 Aβ 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 Aβ1–40 and Aβ1–42 levels (beta=0.163, P<0.001; beta=0.446, P<0.001). This held in subjective memory complainers (SMC) (Aβ1–40; beta=0.208, P=0.017; Aβ1–42; 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-ɛ4 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-ɛ4 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.
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Core funding for this study was provided by CSIRO, which was supplemented by ‘in kind’ contributions from study partners. This research is supported by the Science and Industry Endowment Fund. The AIBL investigators thank Richard Head of CSIRO for initiating and facilitating the AIBL collaboration. The study also received support from the National Health and Medical Research Council via the Dementia Collaborative Research Centres programme. Pfizer International has contributed financial support to assist with the analysis of blood samples and to further the AIBL research programme. The McCusker Alzheimer’s Research Foundation Inc. contributed financial and in kind support to AIBL. We thank all those who took part as subjects in the study for their commitment and dedication to helping advance research into the early detection and causation of AD. The authors acknowledge the financial support of the CRC for Mental Health. The Cooperative Research Centre (CRC) programme is an Australian government initiative.
All authors disclose that Pfizer International has contributed financial support to assist with the analysis of blood samples and to further the AIBL research programme. Ashley Bush discloses that he is a shareholder and paid consultant for Prana Biotechnology Ltd. The authors of this manuscript declare that there are no further actual or potential conflicts. The authors confirm that there are no financial, personal or other relationships with other people or organisations that have inappropriately influenced or biased our work.
Supplementary Information accompanies the paper on the Molecular Psychiatry website
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Verdile, G., Laws, S., Henley, D. et al. Associations between gonadotropins, testosterone and β amyloid in men at risk of Alzheimer’s disease. Mol Psychiatry 19, 69–75 (2014). https://doi.org/10.1038/mp.2012.147
- Alzheimer’s disease
- β amyloid
- luteinizing hormone
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