Development of a plasma biomarker diagnostic model as a screening strategy for Alzheimer's disease in older inpatients

Brain-X Pub Date : 2025-05-28 DOI:10.1002/brx2.70029
Xiaoxia Fang, Zhengke Liu, Xiaojun Kuang, Xiushi Ni, Xu Han, Xuejun Wen, Hong Xu
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Abstract

Neural proteins in the bloodstream have emerged as promising biomarkers for diagnosing Alzheimer's disease (AD). However, their applicability in older individuals and those with multiple co-existing health conditions remains under-investigated. This study evaluated the diagnostic potential of blood-based neuro-markers in participants over 75 years old using an ultra-sensitive single molecule array. We recruited 108 Chinese inpatients with an average age of 92 years, including 30 diagnosed with AD, 46 diagnosed with dementia not caused by AD, and 32 without dementia. Plasma concentrations of amyloid β-40 (Aβ40), amyloid β-42 (Aβ42), tau phosphorylated at threonine 181 (p-tau181), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) in plasma were quantified along with the Aβ42/Aβ40 ratio. Associations between these biomarkers and clinical characteristics (comorbidities and physiological indicators) were examined. Diagnostic models were developed using binary logistic regression based on these neuro-markers. Among the six neuro-markers, p-tau181 exhibited the highest discriminatory power for AD identification, with an area under the curve (AUC) of 0.7731 (95% CI: 0.6493–0.8969). A model combining p-tau181, GFAP, and age achieved an AUC of 0.8654 (95% CI: 0.7762–0.9546), with 75.9% sensitivity and 80.6% specificity in distinguishing AD from individuals without dementia. These findings suggest that plasma biomarkers of neurodegeneration, particularly p-tau181, may hold significant promise as diagnostic tools for AD, even among older patients. The simplified diagnostic model based on plasma neuro-markers offers a feasible approach for AD screening in both clinical and community settings.

Abstract Image

血浆生物标志物诊断模型在老年住院患者阿尔茨海默病筛查中的应用
血液中的神经蛋白已成为诊断阿尔茨海默病(AD)的有希望的生物标志物。然而,它们在老年人和有多种共存健康状况的人中的适用性仍有待调查。本研究使用超灵敏单分子阵列评估了75岁以上参与者血液神经标记物的诊断潜力。我们招募了108名平均年龄为92岁的中国住院患者,其中30名诊断为AD, 46名诊断为非AD引起的痴呆,32名无痴呆。测定血浆中淀粉样蛋白β-40 (Aβ40)、淀粉样蛋白β-42 (Aβ42)、苏氨酸181位点磷酸化的tau蛋白(p-tau181)、神经丝轻链(NfL)和胶质纤维酸性蛋白(GFAP)的浓度,并测定Aβ42/Aβ40比值。研究了这些生物标志物与临床特征(合并症和生理指标)之间的关系。基于这些神经标志物,采用二元逻辑回归建立诊断模型。在6个神经标志物中,p-tau181对AD的鉴别能力最高,曲线下面积(AUC)为0.7731 (95% CI: 0.6493 ~ 0.8969)。结合p-tau181、GFAP和年龄的模型的AUC为0.8654 (95% CI: 0.7762-0.9546),在区分AD和非痴呆个体方面具有75.9%的敏感性和80.6%的特异性。这些发现表明,神经退行性变的血浆生物标志物,特别是p-tau181,可能作为阿尔茨海默病的诊断工具具有重要的前景,即使在老年患者中也是如此。基于血浆神经标志物的简化诊断模型为临床和社区的AD筛查提供了一种可行的方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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