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Title: Associations between gonadotropins, testosterone and β amyloid in men at risk of Alzheimer's disease.
Austin Authors: Verdile, G;Laws, Simon M;Henley, D;Ames, David;Bush, Ashley I;Ellis, Kathryn A;Faux, N G;Gupta, V B;Li, Q-X;Masters, Colin L ;Pike, Kerryn E;Rowe, Christopher C ;Szoeke, Cassandra;Taddei, K;Villemagne, Victor L ;Martins, Ralph N
Institutional Author: AIBL Research Group
Affiliation: Department of Nuclear Medicine & Centre for PET, Austin Health, Heidelberg, Victoria, Australia
Mental Health Research Institute, The University of Melbourne, Parkville, Victoria, Australia
School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, Australia
National Ageing Research Institute, Parkville, Victoria, Australia
Centre for Neuroscience, The University of Melbourne, Parkville, Victoria, Australia
Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia
CSIRO, Parkville, Victoria, Australia
Centre of Excellence for Alzheimer's Disease Research & Care, School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia, Australia
Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia
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
Co-operative Research Centre for Mental Health,
School of Psychological Science, La Trobe University, Bundoora, Victoria Australia
Sir James McCusker Alzheimer's Disease Research Unit (Hollywood Private Hospital), Perth, Western Australia, Australia
Department of Nuclear Medicine & Centre for PET, Austin Health, Heidelberg, Victoria, Australia
Co-operative Research Centre for Mental Health,
Issue Date: 23-Oct-2012
Publication information: Molecular Psychiatry 2012; 19(1): 69-75
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.
DOI: 10.1038/mp.2012.147
Type: Journal Article
Subjects: Aged
Aged, 80 and over
Alzheimer Disease.metabolism.radionuclide imaging
Amyloid beta-Peptides.metabolism
Aniline Compounds.diagnostic use
Apolipoproteins E.genetics
Cohort Studies
Linear Models
Memory Disorders.metabolism.radionuclide imaging
Middle Aged
Mild Cognitive Impairment.metabolism.radionuclide imaging
Neuropsychological Tests
Peptide Fragments.metabolism
Positron-Emission Tomography
Psychiatric Status Rating Scales
Risk Factors
Statistics, Nonparametric
Thiazoles.diagnostic use
Appears in Collections:Journal articles

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