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

G. Verdile, S. M. Laws, D. Henley, D. Ames, A. I. Bush, K. A. Ellis, N. G. Faux, V. B. Gupta, Q. X. Li, C. L. Masters, K. E. Pike, C. C. Rowe, C. Szoeke, K. Taddei, V. L. Villemagne, R. N. Martins*

*Corresponding author for this work

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

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 Aβ 1-40 and not on the more pathogenic Aβ 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 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 Aβ 1-40 and Aβ 1-42 levels (beta=0.163, P<0.001; beta=0.446, P<0.001). This held in subjective memory complainers (SMC) (Aβ 1-40; beta=0.208, P=0.017; Aβ 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-ε4 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-ε4 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.

Original languageEnglish
Pages (from-to)69-75
Number of pages7
JournalMolecular Psychiatry
Volume19
Issue number1
DOIs
Publication statusPublished - Jan 2014
Externally publishedYes

Keywords

  • Alzheimers disease
  • b amyloid
  • luteinizing hormone
  • testosterone

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