A/Prof. Ng Kok Pin, Senior Consultant, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433, Tel: +65 63577153, Email:
J Prev Alzheimers Dis. 2023;10(3):387-400. doi: 10.14283/jpad.2023.53.
The AT(N) framework enables the classification of an individual within the biological Alzheimer's disease (AD) continuum by pairing the cognitive stage with the biomarker status of amyloid-beta (Aβ, A), tau (T) and neurodegeneration (N). AD is a multifactorial disease that may involve different pathogenic mechanisms such as cerebrovascular disease (CVD). Therefore, biomarkers of these mechanisms can be added to the AT(N) framework to enhance the biomarker characterization of individuals within the AD continuum. In AD, white matter hyperintensities (WMH) which are postulated to develop as a result of chronic ischemia from small vessel CVD are shown to play a role in the aetiology. However, the interplay of WMH with Aβ and tau pathophysiology in AD remains unclear. In this review, we summarized the studies that evaluated the associations between WMH and AD pathophysiology (Aβ and tau). We found that the evidence supporting the association of WMH with Aβ was mixed, and this may be explained by the relative contributions of WMH due to its differential load and anatomical distribution. More studies are also needed to determine the association of WMH with tau pathology. Future longitudinal studies with harmonized methodologies to quantify WMH and account for the anatomical differences of WMH are required to validate the relationship between WMH and AT(N) biomarkers. This will allow a clearer understanding of the utility of WMH as a vascular biomarker in the AT(N) framework. Novel CVD biomarkers will also have the potential to further elucidate the contributions of CVD to the AD pathophysiology.
AT(N) 框架通过将认知阶段与淀粉样蛋白-β (Aβ，A)、tau (T) 和神经退行性变 (N) 的生物标志物状态相匹配，使个体在生物阿尔茨海默病 (AD) 连续体中的分类成为可能。AD 是一种多因素疾病，可能涉及不同的发病机制，如脑血管疾病 (CVD)。因此，可以将这些机制的生物标志物添加到 AT(N) 框架中，以增强 AD 连续体中个体的生物标志物特征。在 AD 中，推测由于小血管 CVD 的慢性缺血而发展的脑白质高信号 (WMH) 在发病机制中起作用。然而，WMH 与 AD 中 Aβ 和 tau 病理生理学的相互作用仍不清楚。在这篇综述中，我们总结了评估 WMH 与 AD 病理生理学（Aβ 和 tau）之间关联的研究。我们发现，支持 WMH 与 Aβ 之间关联的证据是混杂的，这可能是由于 WMH 的相对贡献，因为其存在差异的负荷和解剖分布。还需要更多的研究来确定 WMH 与 tau 病理学的关联。需要未来具有量化 WMH 和考虑 WMH 解剖差异的协调方法的纵向研究来验证 WMH 与 AT(N) 生物标志物之间的关系。这将使人们更清楚地了解 WMH 作为 AT(N) 框架中血管生物标志物的实用性。新的 CVD 生物标志物也有可能进一步阐明 CVD 对 AD 病理生理学的贡献。
