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Integrating Serum Biomarkers and Genetic Polymorphisms for Enhanced Alzheimers Disease Risk Screening

Li, Z.; Feng, Z.; He, S.; Tang, H.; Zhao, C.; Liu, J.; Su, Y.; Duan, J.; Tian, X.; Yan, Y.; Shi, X.; Bi, X.

2025-06-19 neurology
10.1101/2025.06.17.25329820 medRxiv
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ObjectiveAnalyze the differences in the detection results of Alzheimers disease (AD) serum biomarkers and the expression of APOE and SLCO1B1 genotypes, then construct an AD diagnostic model integrating serum biomarkers with APOE and SLCO1B1 genotypes to enhance the sensitivity and specificity of AD screening. MethodsSerum samples from 127 participants (41 AD, 39 cognitive impairments, 47 controls) were analyzed for neurofilament light chain (NF), A{beta}42/A{beta}40 ratio, p-TAU231, and p-TAU217 via ELISA, combined with APOE/SLCO1B1 genotyping. A nomogram model was constructed using logistic regression and validated by ROC-AUC and Hosmer-Lemeshow tests. ResultsThe AD group showed elevated NF (p<0.01) and p-TAU231 (p<0.05), reduced A{beta}42/A{beta}40 (p<0.05). APOE {varepsilon}4 homozygotes exhibited the highest p-TAU181 (p<0.001), while SLCO1B1*1b/*1b correlated with increased A{beta}42 (p<0.05). The biomarker model achieved AUC=0.8365, improving to 0.8832 after genetic integration (calibration p>0.05). ConclusionThis study pioneers an AD diagnostic model combining serum p-TAU231, NF, and SLCO1B1 polymorphisms, surpassing single-marker limitations (AUC>0.88). It provides a high-accuracy tool for non-invasive screening and genetic stratification, demonstrating substantial clinical potential.

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