Andrews Elizabeth J, Martini Alessandra C, Head Elizabeth
Department of Pathology and Laboratory Medicine, University of California, Irvine, Irvine, CA, United States.
Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, United States.
Front Neurosci. 2022 Aug 12;16:954999. doi: 10.3389/fnins.2022.954999. eCollection 2022.
Women are disproportionately affected by Alzheimer's disease (AD), yet little is known about sex-specific effects on the development of AD in the Down syndrome (DS) population. DS is caused by a full or partial triplication of chromosome 21, which harbors the amyloid precursor protein (APP) gene, among others. The majority of people with DS in their early- to mid-40s will accumulate sufficient amyloid-beta (Aβ) in their brains along with neurofibrillary tangles (NFT) for a neuropathological diagnosis of AD, and the triplication of the APP gene is regarded as the main cause. Studies addressing sex differences with age and impact on dementia in people with DS are inconsistent. However, women with DS experience earlier age of onset of menopause, marked by a drop in estrogen, than women without DS. This review focuses on key sex differences observed with age and AD in people with DS and a discussion of possible underlying mechanisms that could be driving or protecting from AD development in DS. Understanding how biological sex influences the brain will lead to development of dedicated therapeutics and interventions to improve the quality of life for people with DS and AD.
女性受阿尔茨海默病（AD）的影响尤为严重，但对于唐氏综合征（DS）人群中AD发展的性别特异性影响却知之甚少。DS是由21号染色体的全部或部分三体化引起的，该染色体除其他基因外还包含淀粉样前体蛋白（APP）基因。大多数40岁左右的DS患者大脑中会积累足够的β淀粉样蛋白（Aβ）以及神经原纤维缠结（NFT），从而在神经病理学上被诊断为AD，APP基因的三体化被认为是主要原因。关于DS患者中年龄与性别差异以及对痴呆症影响的研究结果并不一致。然而，与非DS女性相比，DS女性绝经年龄更早，其特征是雌激素水平下降。本综述重点关注DS患者中随年龄增长观察到的关键性别差异，以及对可能驱动或预防DS患者AD发展的潜在机制的讨论。了解生物性别如何影响大脑将有助于开发专门的治疗方法和干预措施，以提高DS和AD患者的生活质量。
