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.
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.
Mol Psychiatry. 2014 Jan;19(1):69-75. doi: 10.1038/mp.2012.147. Epub 2012 Oct 23.
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.
睾酮和促性腺激素与男性认知能力下降以及β淀粉样蛋白（Aβ）代谢的调节有关。相对较少的研究调查了这些激素中的一种或多种变化是否会影响 Aβ 水平，这些研究主要集中在血浆 Aβ（1-40）上，而不是更具致病性的 Aβ（1-42）上。目前，尚无研究调查这些激素是否与生前大脑淀粉样蛋白沉积的增加有关。通过高度特征化的澳大利亚成像、生物标志物和生活方式研究，我们确定了这些激素对血浆 Aβ 水平和大脑淀粉样蛋白负荷（匹兹堡化合物 B（PiB）保留）的影响。对整个队列和亚分类进行了 Spearman 等级相关和线性回归分析。在整个队列中，只有黄体生成素（LH）显示出对血浆 Aβ（1-40）和 Aβ（1-42）水平有显著影响（β=0.163，P<0.001；β=0.446，P<0.001）。在主观记忆抱怨者（SMC）中也是如此（Aβ（1-40）；β=0.208，P=0.017；Aβ（1-42）；β=0.215，P=0.017），但在轻度认知障碍（MCI）和阿尔茨海默病（AD）组中则没有。在 SMC 中，载脂蛋白 E4 等位基因（APOE-ɛ4）的出现频率增加（β=0.536，P<0.001）和血清 LH 水平升高（β=0.421，P=0.004）对 PiB 保留有显著影响。而在 MCI 中，PiB 保留与 APOE-ɛ4 等位基因拷贝数增加（β=0.674，P<0.001）和计算得出的游离睾酮减少（β=-0.303，P=0.043）有关。这些发现表明 LH 和睾酮可能在 AD 的早期临床前阶段逐渐参与其中。此外，在尝试预测疾病的这些最早阶段的 AD 时，应该考虑这些激素。
