Amtage Florian, Birnbaum Dzelila, Reinhard Thomas, Niesen Wolf-Dirk, Weiller Cornelius, Mader Irina, Meyer Philipp T, Rijntjes Michel
Department of Neurology, University Medical Center Freiburg, Germany.
Department of University Eye Hospital Freiburg, Freiburg, Germany.
Case Rep Neurol. 2014 Jun 19;6(2):181-7. doi: 10.1159/000363688. eCollection 2014 May.
We present a patient with chronic postmenopausal estrogen intake with presence of Kayser-Fleischer ring in the cornea and Alzheimer's disease and discuss the pathophysiological mechanisms of estrogen intake and copper accumulation in various tissues, including the central nervous system. Sonography was compatible with copper accumulation in the basal ganglia, but the patient showed no clinical signs of Wilson's disease. Magnetic resonance imaging and positron emission tomography revealed a typical pattern for Alzheimer's disease. We propose increased copper levels as a direct effect of estrogen intake due to an augmented ATP7A-mRNA in the intestine. Moreover, we discuss the impact of elevated free serum copper on accompanying Alzheimer's disease, knowing that copper plays a crucial role in the formation of amyloid plaques and tau aggregation. This might offer a partial explanation for the observation that postmenopausal estrogen therapy is associated with a higher risk of mild cognitive impairment and Alzheimer's disease.
我们报告了一名绝经后长期摄入雌激素的患者,其角膜出现凯-弗环且患有阿尔茨海默病,并讨论了雌激素摄入及铜在包括中枢神经系统在内的各种组织中蓄积的病理生理机制。超声检查结果与基底节区铜蓄积相符,但该患者并无威尔逊病的临床体征。磁共振成像和正电子发射断层扫描显示出阿尔茨海默病的典型特征。我们提出,由于肠道中ATP7A-mRNA增加,雌激素摄入会直接导致铜水平升高。此外,鉴于铜在淀粉样斑块形成和tau蛋白聚集过程中起关键作用,我们还讨论了游离血清铜水平升高对伴发的阿尔茨海默病的影响。这可能为绝经后雌激素治疗与轻度认知障碍和阿尔茨海默病风险较高相关这一观察结果提供部分解释。