. 2014 Jan;19(1):69-75.

doi: 10.1038/mp.2012.147. Epub 2012 Oct 23.

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

G Verdile¹, S M Laws², D Henley³, D Ames⁴, A I Bush⁵, K A Ellis⁶, N G Faux⁷, V B Gupta¹, Q-X Li⁸, C L Masters⁵, K E Pike⁹, C C Rowe¹⁰, C Szoeke¹¹, K Taddei², V L Villemagne¹², R N Martins²; AIBL Research Group

Affiliations

¹ 1] Centre of Excellence for Alzheimer's Disease Research & Care, School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia, Australia [2] Sir James McCusker Alzheimer's Disease Research Unit (Hollywood Private Hospital), Perth, Western Australia, Australia.
² 1] Centre of Excellence for Alzheimer's Disease Research & Care, School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia, Australia [2] Sir James McCusker Alzheimer's Disease Research Unit (Hollywood Private Hospital), Perth, Western Australia, Australia [3] Co-operative Research Centre for Mental Health, http://www.mentalhealthcrc.com.
³ 1] Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia [2] School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, Australia.
⁴ 1] Academic Unit for Psychiatry of Old Age, Department of Psychiatry, The University of Melbourne, St Vincent's Aged Psychiatry Service, St George's Hospital, Melbourne, Victoria, Australia [2] National Ageing Research Institute, Parkville, Victoria, Australia.
⁵ 1] Co-operative Research Centre for Mental Health, http://www.mentalhealthcrc.com [2] Mental Health Research Institute, The University of Melbourne, Parkville, Victoria, Australia [3] Centre for Neuroscience, The University of Melbourne, Parkville, Victoria, Australia.
⁶ 1] Academic Unit for Psychiatry of Old Age, Department of Psychiatry, The University of Melbourne, St Vincent's Aged Psychiatry Service, St George's Hospital, Melbourne, Victoria, Australia [2] National Ageing Research Institute, Parkville, Victoria, Australia [3] Mental Health Research Institute, The University of Melbourne, Parkville, Victoria, Australia.
⁷ 1] Mental Health Research Institute, The University of Melbourne, Parkville, Victoria, Australia [2] Centre for Neuroscience, The University of Melbourne, Parkville, Victoria, Australia.
⁸ 1] Mental Health Research Institute, The University of Melbourne, Parkville, Victoria, Australia [2] Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia.
⁹ 1] Mental Health Research Institute, The University of Melbourne, Parkville, Victoria, Australia [2] Centre for Neuroscience, The University of Melbourne, Parkville, Victoria, Australia [3] Department of Nuclear Medicine & Centre for PET, Austin Health, Heidelberg, Victoria, Australia [4] School of Psychological Science, La Trobe University, Bundoora, Victoria Australia.
¹⁰ Department of Nuclear Medicine & Centre for PET, Austin Health, Heidelberg, Victoria, Australia.
¹¹ 1] National Ageing Research Institute, Parkville, Victoria, Australia [2] CSIRO, Parkville, Victoria, Australia.
¹² 1] Mental Health Research Institute, The University of Melbourne, Parkville, Victoria, Australia [2] Department of Nuclear Medicine & Centre for PET, Austin Health, Heidelberg, Victoria, Australia.

PMID: 23089633
DOI: 10.1038/mp.2012.147

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

G Verdile et al. Mol Psychiatry. 2014 Jan.

. 2014 Jan;19(1):69-75.

doi: 10.1038/mp.2012.147. Epub 2012 Oct 23.

Authors

Affiliations

¹ 1] Centre of Excellence for Alzheimer's Disease Research & Care, School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia, Australia [2] Sir James McCusker Alzheimer's Disease Research Unit (Hollywood Private Hospital), Perth, Western Australia, Australia.
² 1] Centre of Excellence for Alzheimer's Disease Research & Care, School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia, Australia [2] Sir James McCusker Alzheimer's Disease Research Unit (Hollywood Private Hospital), Perth, Western Australia, Australia [3] Co-operative Research Centre for Mental Health, http://www.mentalhealthcrc.com.
³ 1] Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia [2] School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, Australia.
⁴ 1] Academic Unit for Psychiatry of Old Age, Department of Psychiatry, The University of Melbourne, St Vincent's Aged Psychiatry Service, St George's Hospital, Melbourne, Victoria, Australia [2] National Ageing Research Institute, Parkville, Victoria, Australia.
⁵ 1] Co-operative Research Centre for Mental Health, http://www.mentalhealthcrc.com [2] Mental Health Research Institute, The University of Melbourne, Parkville, Victoria, Australia [3] Centre for Neuroscience, The University of Melbourne, Parkville, Victoria, Australia.
⁶ 1] Academic Unit for Psychiatry of Old Age, Department of Psychiatry, The University of Melbourne, St Vincent's Aged Psychiatry Service, St George's Hospital, Melbourne, Victoria, Australia [2] National Ageing Research Institute, Parkville, Victoria, Australia [3] Mental Health Research Institute, The University of Melbourne, Parkville, Victoria, Australia.
⁷ 1] Mental Health Research Institute, The University of Melbourne, Parkville, Victoria, Australia [2] Centre for Neuroscience, The University of Melbourne, Parkville, Victoria, Australia.
⁸ 1] Mental Health Research Institute, The University of Melbourne, Parkville, Victoria, Australia [2] Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia.
⁹ 1] Mental Health Research Institute, The University of Melbourne, Parkville, Victoria, Australia [2] Centre for Neuroscience, The University of Melbourne, Parkville, Victoria, Australia [3] Department of Nuclear Medicine & Centre for PET, Austin Health, Heidelberg, Victoria, Australia [4] School of Psychological Science, La Trobe University, Bundoora, Victoria Australia.
¹⁰ Department of Nuclear Medicine & Centre for PET, Austin Health, Heidelberg, Victoria, Australia.
¹¹ 1] National Ageing Research Institute, Parkville, Victoria, Australia [2] CSIRO, Parkville, Victoria, Australia.
¹² 1] Mental Health Research Institute, The University of Melbourne, Parkville, Victoria, Australia [2] Department of Nuclear Medicine & Centre for PET, Austin Health, Heidelberg, Victoria, Australia.

PMID: 23089633
DOI: 10.1038/mp.2012.147

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

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

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