Irizarry Michael C
Alzheimer Disease Research Unit, Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.
NeuroRx. 2004 Apr;1(2):226-34. doi: 10.1602/neurorx.1.2.226.
Plasma and serum biochemical markers proposed for Alzheimer disease (AD) are based on pathophysiologic processes such as amyloid plaque formation [amyloid beta-protein (A beta), A beta autoantibodies, platelet amyloid precursor protein (APP) isoforms], inflammation (cytokines), oxidative stress (vitamin E, isoprostanes), lipid metabolism (apolipoprotein E, 24S-hydroxycholesterol), and vascular disease [homocysteine, lipoprotein (a)]. Most proteins or metabolites evaluated in plasma or serum thus far are, at best, biological correlates of AD: levels are statistically different in AD versus controls in some cohorts, but they lack sensitivity or specificity for diagnosis or for tracking response to therapy. Approaches combining panels of existing biomarkers or surveying the range of proteins in plasma (proteomics) show promise for discovering biomarker profiles that are characteristic of AD, yet distinct from nondemented patients or patients with other forms of dementia.
为阿尔茨海默病(AD)提出的血浆和血清生化标志物基于淀粉样斑块形成[β-淀粉样蛋白(Aβ)、Aβ自身抗体、血小板淀粉样前体蛋白(APP)异构体]、炎症(细胞因子)、氧化应激(维生素E、异前列腺素)、脂质代谢(载脂蛋白E、24S-羟基胆固醇)和血管疾病[同型半胱氨酸、脂蛋白(a)]等病理生理过程。迄今为止,在血浆或血清中评估的大多数蛋白质或代谢物充其量只是AD的生物学相关指标:在某些队列中,AD患者与对照组相比,其水平在统计学上存在差异,但它们缺乏诊断或跟踪治疗反应所需的敏感性或特异性。结合现有生物标志物组合或检测血浆中蛋白质范围(蛋白质组学)的方法有望发现具有AD特征的生物标志物谱,且与非痴呆患者或其他形式痴呆患者不同。