Currently, over five million Americans suffer with Alzheimer's disease (AD). In the absence of a cure, this number could increase to 13.8 million by 2050. A critical goal of biomedical research is to establish indicators of AD during the preclinical stage (i.e. biomarkers) allowing for early diagnosis and intervention. Numerous advances have been made in developing biomarkers for AD using neuroimaging approaches. These approaches offer tremendous versatility in terms of targeting distinct age-related and pathophysiological mechanisms such as structural decline (e.g. volumetry, cortical thinning), functional decline (e.g. fMRI activity, network correlations), connectivity decline (e.g. diffusion anisotropy), and pathological aggregates (e.g. amyloid and tau PET). In this review, we survey the state of the literature on neuroimaging approaches to developing novel biomarkers for the amnestic form of AD, with an emphasis on combining approaches into multimodal biomarkers. We also discuss emerging methods including imaging epigenetics, neuroinflammation, and synaptic integrity using PET tracers. Finally, we review the complementary information that neuroimaging biomarkers provide, which highlights the potential utility of composite biomarkers as suitable outcome measures for proof-of-concept clinical trials with experimental therapeutics.

中文翻译：

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阿尔茨海默氏病的神经影像生物标志物。

目前，超过五百万美国人患有阿尔茨海默氏病（AD）。在没有治愈方法的情况下，到2050年，这一数字可能会增加到1380万。生物医学研究的一个重要目标是在临床前阶段建立AD指标（即生物标志物），以便及早诊断和干预。使用神经影像学方法开发用于AD的生物标记物已取得了许多进展。这些方法在针对不同的年龄相关和病理生理机制（例如结构下降（例如，容量，皮层变薄），功能下降（例如，fMRI活动，网络相关性），连通性下降（例如，扩散各向异性）和病理聚集体）方面具有巨大的多功能性（例如淀粉样蛋白和tau PET）。在这篇评论中，我们调查有关神经影像学方法以开发针对AD记忆删除形式的新型生物标志物的文献的现状，重点是将方法结合到多峰生物标志物中。我们还将讨论新兴的方法，包括使用PET示踪剂成像表观遗传学，神经炎症和突触完整性。最后，我们回顾了神经影像生物标记物提供的补充信息，突显了复合生物标记物作为适用于实验疗法的概念验证临床试验的合适结果指标的潜在效用。