title: Associations between gonadotropins, testosterone and β amyloid in men at risk of Alzheimer's disease.
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.
authors.affiliation: 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.
authors.forename: G
authors.initials: G
authors.lastname: Verdile
authors.affiliation: 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.
authors.forename: S M
authors.initials: SM
authors.lastname: Laws
authors.affiliation: 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.
authors.forename: D
authors.initials: D
authors.lastname: Henley
authors.affiliation: 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.
authors.forename: D
authors.initials: D
authors.lastname: Ames
authors.affiliation: 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.
authors.forename: A I
authors.initials: AI
authors.lastname: Bush
authors.affiliation: 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.
authors.forename: K A
authors.initials: KA
authors.lastname: Ellis
authors.affiliation: 1] Mental Health Research Institute, The University of Melbourne, Parkville, Victoria, Australia [2] Centre for Neuroscience, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: N G
authors.initials: NG
authors.lastname: Faux
authors.affiliation: 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.
authors.forename: V B
authors.initials: VB
authors.lastname: Gupta
authors.affiliation: 1] Mental Health Research Institute, The University of Melbourne, Parkville, Victoria, Australia [2] Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Q-X
authors.initials: QX
authors.lastname: Li
authors.affiliation: 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.
authors.forename: C L
authors.initials: CL
authors.lastname: Masters
authors.affiliation: 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.
authors.forename: K E
authors.initials: KE
authors.lastname: Pike
authors.affiliation: Department of Nuclear Medicine & Centre for PET, Austin Health, Heidelberg, Victoria, Australia.
authors.forename: C C
authors.initials: CC
authors.lastname: Rowe
authors.affiliation: 1] National Ageing Research Institute, Parkville, Victoria, Australia [2] CSIRO, Parkville, Victoria, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Szoeke
authors.affiliation: 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.
authors.forename: K
authors.initials: K
authors.lastname: Taddei
authors.affiliation: 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.
authors.forename: V L
authors.initials: VL
authors.lastname: Villemagne
authors.affiliation: 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.
authors.forename: R N
authors.initials: RN
authors.lastname: Martins
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds; D001057:Apolipoproteins E / Q000235:genetics; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000378:metabolism; D015331:Cohort Studies; D006062:Gonadotropins / Q000378:metabolism*; D006801:Humans; D016014:Linear Models; D008297:Male; D008569:Memory Disorders / Q000000981:diagnostic imaging / Q000378:metabolism; D008875:Middle Aged; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011569:Psychiatric Status Rating Scales; D012307:Risk Factors; D018709:Statistics, Nonparametric; D013739:Testosterone / Q000378:metabolism*; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D001057:Apolipoproteins E; D006062:Gonadotropins; D010446:Peptide Fragments; D013844:Thiazoles; C075222:amyloid beta-protein (1-42); D013739:Testosterone