Down syndrome (DS) is the main genetic cause of intellectual disability worldwide. The overexpression of the Amyloid Precursor Protein, present in chromosome 21, leads to β‐amyloid deposition that results in Alzheimer disease (AD) and, in most cases, also to cerebral amyloid angiopathy (CAA) neuropathology. People with DS invariably develop the neuropathological hallmarks of AD at the age of 40, and they are at an ultra high risk for suffering AD‐related cognitive impairment thereafter. In the general population, cerebrovascular disease is a significant contributor to AD‐related cognitive impairment, while in DS remains understudied. This review describes the current knowledge on cerebrovascular disease in DS and reviews the potential biomarkers that could be useful in the future studies, focusing on CAA. We also discuss available evidence on sporadic AD or other genetically determined forms of AD. We highlight the urgent need of large biomarker‐characterized cohorts, including neuropathological correlations, to study the exact contribution of CAA and related vascular factors that play a role in cognition and occur with aging, their characterization and interrelationships. DS represents a unique context in which to perform these studies as this population is relatively protected from some conventional vascular risk factors and they develop significant CAA, DS represents a particular atheroma‐free model to study AD‐related vascular pathologies. Only deepening on these underlying mechanisms, new preventive and therapeutic strategies could be designed to improve the quality of life of this population and their caregivers and lead to new avenues of treatment also in the general AD population.

中文翻译：

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唐氏综合症，阿尔茨海默氏病和脑淀粉样血管病：脑淀粉样变性的复杂三角形。

唐氏综合症（DS）是全球智力障碍的主要原因。存在于21号染色体中的淀粉样前体蛋白的过表达导致β-淀粉样蛋白沉积，从而导致阿尔茨海默氏病（AD），并且在大多数情况下还导致脑淀粉样蛋白血管病（CAA）神经病理学。患有DS的人在40岁时总是出现AD的神经病理学特征，并且此后患AD相关的认知障碍的风险极高。在一般人群中，脑血管疾病是与AD相关的认知障碍的重要原因，而在DS中，其研究仍很不足。这篇综述描述了DS中有关脑血管疾病的当前知识，并综述了可能对将来的研究有用的潜在生物标志物，重点是CAA。我们还将讨论有关散发性AD或其他遗传确定的AD形式的可用证据。我们强调了迫切需要大型生物标志物表征的队列，包括神经病理学相关性，以研究CAA和相关血管因子在认知中发挥作用并与衰老，它们的特征和相互关系有关的确切作用。DS代表了开展这些研究的独特背景，因为该人群相对不受某些常规血管危险因素的影响，并且它们会形成明显的CAA，DS代表一种特定的无动脉粥样硬化模型来研究与AD相关的血管病理。只有深化这些潜在的机制，