身体状况对血浆p-tau217和p-tau217/Aβ42诊断准确性的影响。
Influence of medical conditions on the diagnostic accuracy of plasma p-tau217 and p-tau217/Aβ42.
作者信息
Olvera-Rojas Marcos, Sewell Kelsey R, Karikari Thomas K, Huang Haiqing, Oberlin Lauren E, Zeng Xuemei, Morris Jill K, Collins Audrey M, Drake Jermon A, Sutton Bradley P, Kramer Arthur F, Hillman Charles H, Vidoni Eric D, Burns Jeffrey M, Kamboh M Ilyas, McAuley Edward, Marsland Anna L, Chen Yijun, Lafferty Tara K, Sehrawat Anuradha, Jakicic John M, Wan Lu, Kang Chaeryon, Erickson Kirk I
机构信息
Department of Physical Education and Sports, Faculty of Sport Sciences, Sport and Health University Research Institute (iMUDS), University of Granada, Granada, Spain.
AdventHealth Research Institute, Orlando, Florida, USA.
出版信息
Alzheimers Dement. 2025 Feb;21(2):e14430. doi: 10.1002/alz.14430. Epub 2024 Dec 6.
INTRODUCTION
Blood-based biomarkers (BBMs) can enable early detection of brain amyloid beta (Aβ) pathology in cognitively unimpaired individuals. However, the extent to which common medical conditions affect biomarker performance remains unclear.
METHODS
Participants (n = 348) included individuals without cognitive impairment. We studied how brain Aβ associated with BBMs (Aβ42/40, phosphorylated tau [p-tau] 181 and 217, p-tau217/Aβ42, glial fibrillary acidic protein [GFAP], and neurofilament light [NfL]) and optimal BBM thresholds for predicting brain Aβ positivity and whether they are obscured by the presence of common medical conditions.
RESULTS
Plasma Aβ42/40, p-tau181, p-tau217, and GFAP, but not NfL, were significantly associated with brain Aβ. P-tau217/Aβ42 showed the best discriminative performance (area under the curve: 0.91). The strength of p-tau217-brain Aβ associations were obscured by diabetes and cardiovascular conditions.
DISCUSSION
These results suggest BBMs may help detect early Aβ pathology but suggest caution in their use due to common medical conditions that could affect accuracy.
HIGHLIGHTS
Plasma Aβ42/40, p-tau181, p-tau217, and GFAP but not NfL showed significant associations with brain Aβ. BBMs were more strongly associated with the level of brain Aβ in those without diabetes and cardiovascular conditions. P-tau217/Aβ42 showed the best performance (AUC = 0.91) in discriminating Aβ presence with an optimal cut-off of >1.2, followed by p-tau217 at >0.46 pg/mL, with performance slightly improving when excluding participants with cardiovascular conditions.
引言
基于血液的生物标志物（BBMs）能够在认知未受损个体中实现脑淀粉样β蛋白（Aβ）病理的早期检测。然而，常见医疗状况对生物标志物性能的影响程度仍不清楚。
方法
参与者（n = 348）包括无认知障碍的个体。我们研究了脑Aβ与BBMs（Aβ42/40、磷酸化tau蛋白[p-tau]181和217、p-tau217/Aβ42、胶质纤维酸性蛋白[GFAP]和神经丝轻链蛋白[NfL]）之间的关联，以及预测脑Aβ阳性的最佳BBM阈值，以及它们是否会因常见医疗状况的存在而受到影响。
结果
血浆Aβ42/40、p-tau181、p-tau217和GFAP与脑Aβ显著相关，但NfL与脑Aβ无显著关联。P-tau217/Aβ42表现出最佳的鉴别性能（曲线下面积：0.91）。糖尿病和心血管疾病会掩盖p-tau217与脑Aβ关联的强度。
讨论
这些结果表明BBMs可能有助于检测早期Aβ病理，但由于可能影响准确性的常见医疗状况，在使用时需谨慎。
要点
血浆Aβ42/40、p-tau181、p-tau217和GFAP与脑Aβ显著相关，但NfL与脑Aβ无显著关联。在无糖尿病和心血管疾病的个体中，BBMs与脑Aβ水平的关联更强。P-tau217/Aβ42在鉴别Aβ存在方面表现最佳（AUC = 0.91），最佳截断值>1.2，其次是p-tau217>0.46 pg/mL，排除心血管疾病参与者后性能略有改善。
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