Department of Pediatrics and Neurology, School of Medicine, University of California, Irvine, CA, USA.
Sanders Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
Nat Rev Neurol. 2019 Mar;15(3):135-147. doi: 10.1038/s41582-018-0132-6.
Virtually all adults with Down syndrome (DS) show the neuropathological changes of Alzheimer disease (AD) by the age of 40 years. This association is partially due to overexpression of amyloid precursor protein, encoded by APP, as a result of the location of this gene on chromosome 21. Amyloid-β accumulates in the brain across the lifespan of people with DS, which provides a unique opportunity to understand the temporal progression of AD and the epigenetic factors that contribute to the age of dementia onset. This age dependency in the development of AD in DS can inform research into the presentation of AD in the general population, in whom a longitudinal perspective of the disease is not often available. Comparison of the risk profiles, biomarker profiles and genetic profiles of adults with DS with those of individuals with AD in the general population can help to determine common and distinct pathways as well as mechanisms underlying increased risk of dementia. This Review evaluates the similarities and differences between the pathological cascades and genetics underpinning DS and AD with the aim of providing a platform for common exploration of these disorders.
几乎所有患有唐氏综合征（Down syndrome，DS）的成年人在 40 岁时都会出现阿尔茨海默病（Alzheimer disease，AD）的神经病理学变化。这种关联部分归因于淀粉样前体蛋白（amyloid precursor protein，APP）的过度表达，这是由于该基因位于 21 号染色体上。淀粉样β在 DS 患者的整个生命周期中在大脑中积累，这为了解 AD 的时间进展以及导致痴呆发病年龄的表观遗传因素提供了独特的机会。AD 在 DS 中的这种年龄依赖性发展可以为研究一般人群中 AD 的表现提供信息，因为在一般人群中，AD 的纵向观点并不常见。比较 DS 患者与一般人群中 AD 患者的风险概况、生物标志物概况和遗传概况，可以帮助确定共同和独特的途径以及导致痴呆风险增加的机制。本综述评估了 DS 和 AD 背后的病理级联和遗传学的相似之处和不同之处，旨在为这些疾病的共同探索提供一个平台。
