Collaborative Drug Discovery Research (CDDR) and Brain Degeneration and Therapeutics Research Group, Faculty of Pharmacy, University Teknologi MARA (UiTM) Cawangan Selangor, Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia.
Division of Geriatric Medicine, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Int J Neurosci. 2022 Oct;132(10):1014-1025. doi: 10.1080/00207454.2020.1860038. Epub 2020 Dec 15.
Alzheimer's disease (AD), the commonest form of dementia which is characterized by progressive decline in cognitive function, can only be definitively diagnosed after death. Although biomarkers may aid diagnosis, currently available AD biomarkers, which are predominantly based on cerebrospinal fluid and neuroimaging facilities, are either invasive or costly. Blood-based biomarkers for AD diagnosis are highly sought after due to its practicality at the clinic. This study was undertaken to determine the differential protein expression in plasma amongst Malaysian AD, mild cognitive impairment (MCI) and non-AD individuals. A proteomic approach which utilized two-dimensional differential in gel electrophoresis (2 D DIGE) was performed for blood samples from 15 AD, 14 MCI and 15 non-AD individuals. Mass spectrometry (MS)-based protein identification via MALDI ToF/ToF showed that fibrinogen-β-chain (spot 64) and fibrinogen-γ-chain (spot 91) with differential expression ratio >1.5 were significantly upregulated ( < 0.05) in AD patients when compared to non-AD individuals. Further data analysis using Pearson correlation found that the upregulated fibrinogen-γ-chain was weakly but significantly ( < 0.05) and inversely correlated with cognitive decline. Fibrinogen isoforms may play important roles in the vascular pathology of AD as well as neuroinflammation. As such, fibrinogen appears to be a promising blood-based biomarker for AD. Further validation of the present findings in larger population is now warranted.
阿尔茨海默病（AD）是最常见的痴呆症形式，其特征是认知功能进行性下降，只能在死后才能明确诊断。虽然生物标志物可以辅助诊断，但目前可用的 AD 生物标志物主要基于脑脊液和神经影像学设施，要么具有侵入性，要么成本高昂。由于在临床实践中的实用性，人们非常希望找到用于 AD 诊断的基于血液的生物标志物。本研究旨在确定马来西亚 AD、轻度认知障碍（MCI）和非 AD 个体血浆中差异表达的蛋白质。 我们采用二维差异凝胶电泳（2D DIGE）的蛋白质组学方法对 15 名 AD、14 名 MCI 和 15 名非 AD 个体的血液样本进行了分析。 通过基质辅助激光解吸电离飞行时间/飞行时间（MALDI ToF/ToF）的 MS 基于蛋白质鉴定显示，纤维蛋白原-β 链（斑点 64）和纤维蛋白原-γ 链（斑点 91）的差异表达比率>1.5 在 AD 患者中明显上调（<0.05）与非 AD 个体相比。 使用 Pearson 相关性的进一步数据分析发现，上调的纤维蛋白原-γ 链与认知能力下降呈弱但显著（<0.05）负相关。 纤维蛋白原异构体可能在 AD 的血管病理学和神经炎症中起重要作用。 因此，纤维蛋白原似乎是一种很有前途的 AD 基于血液的生物标志物。 现在需要在更大的人群中进一步验证本研究的发现。
