Anti-Amyloid Therapy, AD, and ARIA: Untangling the Role of CAA.
Anti-Amyloid Therapy, AD, and ARIA: Untangling the Role of CAA.
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DOI：
10.3390/jcm12216792
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发表时间：
2023-10-27
影响因子：
3.9
通讯作者：
Hajjar I
中科院分区：
文献类型：
--
作者：
Sin MK;Zamrini E;Ahmed A;Nho K;Hajjar I
抗淀粉样蛋白治疗（AAT），如抗淀粉样蛋白单克隆抗体，是早期阿尔茨海默病（AD）患者的新兴治疗方法。AAT靶向脑中的淀粉样蛋白β斑块。淀粉样蛋白相关成像异常（ARIA），即AD患者脑磁共振成像（MRI）上观察到的异常信号，可能自发发生，但更频繁地发生为AAT的副作用。脑淀粉样血管病（CAA）是ARIA的主要危险因素。β淀粉样蛋白在AD和CAA的发病机制中起关键作用。淀粉样蛋白β在脑实质中作为斑块积聚是AD的病理学标志，而淀粉样蛋白β在脑血管中积聚导致CAA。更好地了解ARIA的病理生理学对于早期发现高危人群是必要的。这可能导致改善风险分层和最终减少症状性ARIA。通过脑活检或尸检对CAA进行组织病理学确认是金标准，但在临床上并不可行。MRI是一种可用于检测CAA的体内工具。脑脊液淀粉样蛋白β水平检测和淀粉样蛋白PET成像可用，但不能提供CAA与AD中淀粉样蛋白斑块的特异性。因此，开发和测试生物标志物作为CAA存在和严重程度的可靠和敏感的筛查工具是减少ARIA并发症的优先事项。
Anti-amyloid therapies (AATs), such as anti-amyloid monoclonal antibodies, are emerging treatments for people with early Alzheimer’s disease (AD). AATs target amyloid β plaques in the brain. Amyloid-related imaging abnormalities (ARIA), abnormal signals seen on magnetic resonance imaging (MRI) of the brain in patients with AD, may occur spontaneously but occur more frequently as side effects of AATs. Cerebral amyloid angiopathy (CAA) is a major risk factor for ARIA. Amyloid β plays a key role in the pathogenesis of AD and of CAA. Amyloid β accumulation in the brain parenchyma as plaques is a pathological hallmark of AD, whereas amyloid β accumulation in cerebral vessels leads to CAA. A better understanding of the pathophysiology of ARIA is necessary for early detection of those at highest risk. This could lead to improved risk stratification and the ultimate reduction of symptomatic ARIA. Histopathological confirmation of CAA by brain biopsy or autopsy is the gold standard but is not clinically feasible. MRI is an available in vivo tool for detecting CAA. Cerebrospinal fluid amyloid β level testing and amyloid PET imaging are available but do not offer specificity for CAA vs amyloid plaques in AD. Thus, developing and testing biomarkers as reliable and sensitive screening tools for the presence and severity of CAA is a priority to minimize ARIA complications.
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