Department of Internal Medicine, The University of Arizona College of Medicine-Phoenix, Phoenix, AZ 85004, USA.
Chemical Engineering, School for Engineering of Matter, Transport and Energy, Arizona State University, Tempe, AZ 85287, USA.
Int J Mol Sci. 2022 Dec 10;23(24):15670. doi: 10.3390/ijms232415670.
Blood-based biomarkers are needed for the early diagnosis of Alzheimer's disease (AD). We analyzed longitudinal human plasma samples from AD and control cases to identify biomarkers for the early diagnosis of AD. Plasma samples were grouped based on clinical diagnosis at the time of collection: AD, mild cognitive impairment (MCI), and pre-symptomatic (preMCI). Samples were analyzed by ELISA using a panel of reagents against nine different AD-related amyloid-β (Aβ), tau, or TDP-43 variants. Receiver operating characteristic (ROC) curves of different biomarker panels for different diagnostic sample groups were determined. Analysis of all of the samples gave a sensitivity of 92% and specificity of 76% for the diagnosis of AD. Early-stage diagnosis of AD, utilizing only the preMCI and MCI samples, identified 88% of AD cases. Using sex-biased biomarker panels, early diagnosis of AD cases improved to 96%. Using the sex-biased panels, we also identified 6 of the 25 control group cases as being at high risk of AD, which is consistent with what is expected given the advanced age of the control cases. Specific AD-associated protein variants are effective blood-based biomarkers for the early diagnosis of AD. Notably, significant differences were observed in biomarker profiles for the early detection of male and female AD cases.
用于阿尔茨海默病（AD）早期诊断的基于血液的生物标志物。我们分析了 AD 和对照组患者的纵向人类血浆样本，以确定 AD 早期诊断的生物标志物。根据采集时的临床诊断对血浆样本进行分组：AD、轻度认知障碍（MCI）和无症状前（preMCI）。使用针对 9 种不同 AD 相关淀粉样蛋白-β（Aβ）、tau 或 TDP-43 变体的试剂组合，通过 ELISA 分析样本。确定了不同诊断样本组不同生物标志物组合的接收者操作特征（ROC）曲线。对所有样本的分析对 AD 的诊断得出了 92%的灵敏度和 76%的特异性。仅利用 preMCI 和 MCI 样本进行 AD 的早期诊断，可识别 88%的 AD 病例。使用基于性别的生物标志物组合，AD 病例的早期诊断提高到 96%。使用基于性别的面板，我们还鉴定出 25 名对照组病例中有 6 名具有较高的 AD 风险，这与对照组病例年龄较大的预期相符。特定的 AD 相关蛋白变体是 AD 早期诊断的有效基于血液的生物标志物。值得注意的是，在检测男性和女性 AD 病例的早期，观察到生物标志物谱存在显著差异。
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