Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.
IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
Nat Med. 2022 Sep;28(9):1797-1801. doi: 10.1038/s41591-022-01925-w. Epub 2022 Aug 11.
Blood biomarkers indicating elevated amyloid-β (Aβ) pathology in preclinical Alzheimer's disease are needed to facilitate the initial screening process of participants in disease-modifying trials. Previous biofluid data suggest that phosphorylated tau231 (p-tau231) could indicate incipient Aβ pathology, but a comprehensive comparison with other putative blood biomarkers is lacking. In the ALFA+ cohort, all tested plasma biomarkers (p-tau181, p-tau217, p-tau231, GFAP, NfL and Aβ42/40) were significantly changed in preclinical Alzheimer's disease. However, plasma p-tau231 reached abnormal levels with the lowest Aβ burden. Plasma p-tau231 and p-tau217 had the strongest association with Aβ positron emission tomography (PET) retention in early accumulating regions and associated with longitudinal increases in Aβ PET uptake in individuals without overt Aβ pathology at baseline. In summary, plasma p-tau231 and p-tau217 better capture the earliest cerebral Aβ changes, before overt Aβ plaque pathology is present, and are promising blood biomarkers to enrich a preclinical population for Alzheimer's disease clinical trials.
血液生物标志物可用于指示临床前阿尔茨海默病中淀粉样蛋白-β（Aβ）病理的升高，从而有助于对疾病修饰试验参与者进行初步筛选。先前的生物流体数据表明，磷酸化 tau231（p-tau231）可能指示 Aβ 病理的早期发生，但缺乏与其他潜在血液生物标志物的全面比较。在 ALFA+队列中，所有测试的血浆生物标志物（p-tau181、p-tau217、p-tau231、GFAP、NfL 和 Aβ42/40）在临床前阿尔茨海默病中均发生显著改变。然而，血浆 p-tau231 在 Aβ 负担最低时达到异常水平。血浆 p-tau231 和 p-tau217 与 Aβ 正电子发射断层扫描（PET）在早期积累区域的保留具有最强的相关性，并与基线时无明显 Aβ 病理个体的 Aβ PET 摄取的纵向增加相关。总之，血浆 p-tau231 和 p-tau217 更好地捕捉到了最早的脑 Aβ 变化，即在明显的 Aβ 斑块病理出现之前，并且是一种有前途的血液生物标志物，可用于丰富临床前人群进行阿尔茨海默病临床试验。
