Lim Siong Meng, Ng Yee Ling, Majeed Abu Bakar Abdul, Tan Maw Pin, Khor Hui Min, Kamaruzzaman Shahrul Bahyah, Ramasamy Kalavathy
Collaborative Drug Discovery Research (CDDR) Group, Faculty of Pharmacy, Universiti Teknologi MARA (UiTM) Cawangan Selangor, Selangor Darul Ehsan, Kampus Puncak Alam, 42300, Bandar Puncak Alam, Malaysia.
Brain Degeneration and Therapeutics Group, Faculty of Pharmacy, University Teknologi MARA (UiTM) Cawangan Selangor, Selangor Darul Ehsan, Kampus Puncak Alam, 42300, Bandar Puncak Alam, Malaysia.
Geroscience. 2024 Dec 9. doi: 10.1007/s11357-024-01462-z.
The present study explored for the first time the blood-based proteomic signature that could potentially distinguish older adults with and without cognitive frailty (CF). The participants were recruited under the Malaysian Elders Longitudinal Research (MELoR) study. Cognition and physical frailty were determined using the Montreal Cognitive Assessment (MoCA) and Fried's criteria, respectively. The differential protein expression in the blood samples (38 CF vs 40 robust) were then determined using the Sequential Window Acquisition of All Theoretical Mass Spectra (SWATH) analysis. A total of 294 proteins were found to be differentially expressed in the CF group as opposed to the robust group. Considering proteins with fold change (FC) ≥ ± 2 and p-values < 0.05, 13 proteins were significantly upregulated and nine proteins significantly downregulated in the CF group when compared to the robust group. Subsequent correlation analysis identified nine dysregulated proteins, namely APOA1, APOA2, APOA4, APOC1, APOE, GPX3, RBP4, SERPINC1 and TTR, to exhibit significantly and moderately strong correlations with parameters of cognitive and/or frailty assessments. These proteins could potentially serve as useful proteomic signature of CF given their sensitivity > 78%, specificity > 75%, accuracy > 80% and area under the curve (AUC) > 0.8. The major biological pathways that could be potentially dysregulated by the nine proteins were associated with lipid metabolism and the retinoid system. The present findings warrant further validation in future studies that involve a larger cohort.
本研究首次探索了基于血液的蛋白质组学特征，该特征有可能区分有和没有认知衰弱（CF）的老年人。参与者是在马来西亚老年人纵向研究（MELoR）中招募的。分别使用蒙特利尔认知评估（MoCA）和弗里德标准来确定认知和身体衰弱情况。然后使用全理论质谱的顺序窗口采集（SWATH）分析来确定血液样本（38例CF患者与40例健康对照）中的差异蛋白表达。与健康对照组相比，共发现294种蛋白质在CF组中差异表达。考虑到倍数变化（FC）≥±2且p值<0.05，与健康对照组相比，CF组中有13种蛋白质显著上调，9种蛋白质显著下调。随后的相关性分析确定了9种失调蛋白，即载脂蛋白A1（APOA1）、载脂蛋白A2（APOA2）、载脂蛋白A4（APOA4）、载脂蛋白C1（APOC1）、载脂蛋白E（APOE）、谷胱甘肽过氧化物酶3（GPX3）、视黄醇结合蛋白4（RBP4）、丝氨酸蛋白酶抑制剂C1（SERPINC1）和甲状腺素转运蛋白（TTR），它们与认知和/或衰弱评估参数表现出显著且中等强度的相关性。鉴于这些蛋白质的敏感性>78%、特异性>75%、准确性>80%且曲线下面积（AUC）>0.8，它们有可能作为CF有用的蛋白质组学特征。这9种蛋白质可能失调的主要生物学途径与脂质代谢和视黄醇系统有关。本研究结果有待在未来涉及更大队列的研究中进一步验证。
