脑脊液中 Aβ37/42 肽比值作为阿尔茨海默病 Aβ标志物的改进。
Identification of the Aβ37/42 peptide ratio in CSF as an improved Aβ biomarker for Alzheimer's disease.
机构信息
Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Department of Medicinal Chemistry, University of Kansas, Lawrence, Kansas, USA.
出版信息
Alzheimers Dement. 2023 Jan;19(1):79-96. doi: 10.1002/alz.12646. Epub 2022 Mar 12.
INTRODUCTION
Identifying CSF-based biomarkers for the β-amyloidosis that initiates Alzheimer's disease (AD) could provide inexpensive and dynamic tests to distinguish AD from normal aging and predict future cognitive decline.
METHODS
We developed immunoassays specifically detecting all C-terminal variants of secreted amyloid β-protein and identified a novel biomarker, the Aβ 37/42 ratio, that outperforms the canonical Aβ42/40 ratio as a means to evaluate the γ-secretase activity and brain Aβ accumulation.
RESULTS
We show that Aβ 37/42 can distinguish physiological and pathological status in (1) presenilin-1 mutant vs wild-type cultured cells, (2) AD vs control brain tissue, and (3) AD versus cognitively normal (CN) subjects in CSF, where 37/42 (AUC 0.9622) outperformed 42/40 (AUC 0.8651) in distinguishing CN from AD.
DISCUSSION
We conclude that the Aβ 37/42 ratio sensitively detects presenilin/γ-secretase dysfunction and better distinguishes CN from AD than Aβ42/40 in CSF. Measuring this novel ratio alongside promising phospho-tau analytes may provide highly discriminatory fluid biomarkers for AD.
简介
识别引发阿尔茨海默病（AD）的β-淀粉样蛋白的脑脊液生物标志物，可以提供廉价且动态的测试，以区分 AD 与正常衰老，并预测未来的认知能力下降。
方法
我们专门开发了可检测所有分泌型淀粉样β蛋白 C 端变体的免疫分析，确定了一种新的生物标志物，即 Aβ 37/42 比值，它优于经典的 Aβ42/40 比值，可作为评估 γ-分泌酶活性和脑内 Aβ 聚集的手段。
结果
我们表明，Aβ 37/42 可以区分（1）早老素-1 突变体与野生型培养细胞、（2）AD 与对照脑组织、（3）CSF 中 AD 与认知正常（CN）个体的生理和病理状态，其中 37/42（AUC 0.9622）在区分 CN 与 AD 方面优于 42/40（AUC 0.8651）。
讨论
我们得出结论，Aβ 37/42 比值灵敏地检测早老素/γ-分泌酶功能障碍，与 CSF 中的 Aβ42/40 相比，更好地区分 CN 与 AD。与有前途的磷酸化 tau 分析物一起测量该新比值可能为 AD 提供高度区分性的液体生物标志物。
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