Age-related neurodegeneration characteristic of late-onset Alzheimer's disease (LOAD) begins in middle age, well before symptoms. Translational models to identify modifiable risk factors are needed to understand etiology and identify therapeutic targets. Here, we outline the evidence supporting the vervet monkey (Chlorocebus aethiops sabaeus) as a model of aging-related AD-like neuropathology and associated phenotypes including cognitive function, physical function, glucose handling, intestinal physiology, and CSF, blood, and neuroimaging biomarkers. This review provides the most comprehensive multisystem description of aging in vervets to date. This review synthesizes a large body of evidence that suggests that aging vervets exhibit a coordinated suite of traits consistent with early AD and provide a powerful, naturally occurring model for LOAD. Notably, relationships are identified between AD-like neuropathology and modifiable risk factors. Gaps in knowledge and key limitations are provided to shape future studies to illuminate mechanisms underlying divergent neurocognitive aging trajectories and to develop interventions that increase resilience to aging-associated chronic disease, particularly, LOAD.

中文翻译：

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圈养黑长尾猴（Chlorocebus aethiops sabaeus）中与衰老相关的阿尔茨海默病样神经病理学和功能下降

晚发性阿尔茨海默病 (LOAD) 的年龄相关神经退行性变特征始于中年，远早于出现症状。需要识别可改变的危险因素的转化模型来了解病因并确定治疗靶点。在这里，我们概述了支持黑长尾猴（Chlorocebus aethiops sabaeus）作为衰老相关 AD 样神经病理学模型的证据以及相关表型，包括认知功能、身体功能、葡萄糖处理、肠道生理学以及脑脊液、血液和神经影像生物标志物。这篇综述提供了迄今为止最全面的长尾黑颚猴衰老的多系统描述。这篇综述综合了大量证据，表明衰老的长尾黑颚猴表现出与早期 AD 一致的一系列协调特征，并为 LOAD 提供了一个强大的、自然发生的模型。值得注意的是，AD 样神经病理学与可改变的危险因素之间的关系已被确定。知识差距和关键局限性有助于未来的研究，以阐明不同神经认知衰老轨迹的潜在机制，并制定干预措施，提高对与衰老相关的慢性疾病（特别是 LOAD）的抵抗力。