Gulati Jaskeerat S, Pedretti Rose, Hendren Nicholas, Kozlitina Julia, Saelices Lorena, Roth Lori R, Grodin Justin L
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Department of Biophysics, Center for Alzheimer's and Neurodegenerative Diseases, Peter O'Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Curr Heart Fail Rep. 2025 Feb 13;22(1):8. doi: 10.1007/s11897-025-00696-y.
The most common type of cardiac amyloidosis is transthyretin amyloidosis (ATTR-CM). Early forms of the disease can often go undetected. Effective pharmacological treatments are available for ATTR-CM. However, current treatment options may be more effective when used earlier in the disease, making early detection paramount. Below, we discuss updates with regards to the role that blood-based biomarkers play in detecting subclinical cardiac amyloidosis.
Carriers of amyloidogenic mutations in the TTR gene are at a heightened risk of developing heart failure and have higher mortality rates compared with noncarrier counterparts. Conventional biomarkers, such as the cardiac troponins and natriuretic peptides, may be useful to monitor subclinical cardiac amyloidosis. In addition, recent studies have demonstrated links between amyloidogenic TTR carrier status and low levels of circulating transthyretin (TTR) and retinol-binding protein 4 (RBP4). Laboratory advances have also allowed for the development of peptide-based detection methods. Probes targeting transthyretin aggregates and nonnative TTR peptides have shown promise in differentiating ATTR from non-ATTR amyloidosis populations. Finally, recent studies have identified neurofilament light chains as potential biomarkers for detecting polyneuropathy-predominant amyloidosis. Conventional biomarkers, such as cardiac troponin and natriuretic peptides may indicate evolving amyloid deposition in early ATTR-CM. However, they are non-specific and emerging biomarkers such as serum transthyretin levels, retinol-binding protein 4, transthyretin aggregates, nonnative TTR, and neurofilament light chains may hold promise in characterizing subclinical ATTR.
最常见的心脏淀粉样变性类型是转甲状腺素蛋白淀粉样变性（ATTR-CM）。该病的早期形式常常难以被发现。ATTR-CM有有效的药物治疗方法。然而，目前的治疗方案若在疾病早期使用可能会更有效，因此早期检测至关重要。下面，我们将讨论血液生物标志物在检测亚临床心脏淀粉样变性中所起作用的相关进展。
转甲状腺素蛋白（TTR）基因中淀粉样变基因突变的携带者发生心力衰竭的风险增加，与非携带者相比死亡率更高。传统生物标志物，如心肌肌钙蛋白和利钠肽，可能有助于监测亚临床心脏淀粉样变性。此外，最近的研究表明淀粉样变TTR携带者状态与循环转甲状腺素蛋白（TTR）和视黄醇结合蛋白4（RBP4）水平低之间存在联系。实验室技术的进步也使得基于肽的检测方法得以发展。靶向转甲状腺素蛋白聚集体和非天然TTR肽的探针在区分ATTR与非ATTR淀粉样变性人群方面显示出前景。最后，最近的研究已将神经丝轻链确定为检测以多发性神经病为主的淀粉样变性的潜在生物标志物。传统生物标志物，如心肌肌钙蛋白和利钠肽，可能表明早期ATTR-CM中淀粉样沉积的进展。然而，它们是非特异性的，而血清转甲状腺素蛋白水平、视黄醇结合蛋白4、转甲状腺素蛋白聚集体、非天然TTR和神经丝轻链等新兴生物标志物可能在表征亚临床ATTR方面具有前景。
