据不完全统计,在英国一国就大约有820,000多名阿尔茨海默氏症(AD)患者,阿尔茨海默氏症是导致老年人痴呆的最普遍原因。就目前来说,如何正确区分阿尔茨海默氏症导致的记忆力减弱和因年龄增大导致记忆减弱是比较困难的。
近日,英国诺丁汉大学的研究人员在Alzheimer's Disease杂志上发表论文称:脑脊液中存在的七种异常蛋白或许可以作为AD患者发病早期的诊断生物标志物。
阿尔茨海默氏症被早期诊断出来后有助于及时进行干预治疗,从而在最大程度上治愈患者。该论文的主要研究者丁汉大学人类基因组学和分子遗传学教授--凯文-摩根表示:该研究结果确确实为提高早期诊断阿尔茨海默氏症提供了可能。
研究人员抽取了33名阿尔茨海默氏症患者、10名轻度认知功能障碍患者以及20名正常老年人的脑脊液样本并进行了相关分析。工作人员在分析了每个样品中的蛋白质后发现阿尔茨海默氏症患者的脑脊液样品有四种蛋白含量显著增高,有三种蛋白含量则出现了减少趋势。
早期研究发现一种叫做SPARCL1的蛋白是阿尔茨海默氏症患者诊断的最好生物标志物,在该研究中,假如研究者光检测脑脊液样品中SPARCL1蛋白后,SPARCL1蛋白预示阿尔茨海默氏症的精确性只有65%,而当联合利用上述七种生物标志物时精确度可以达到95%。
研究人员表示在接下来的研究中我们很有必要重点探究阿尔茨海默氏症患者体内是什么原因导致了这几种蛋白发生了变化,只有了解引起变化的原因我们才能对阿尔茨海默氏症患者进行更好的研究治疗。(生物谷Bioon.com)
doi:10.3233/JAD-2011-111505
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Identification of SPARC-like 1 Protein as Part of a Biomarker Panel for Alzheimer's Disease in Cerebrospinal Fluid
Baharak Vafadar-Isfahani1, Graham Ball1, Clare Coveney1, Christophe Lemetre1, David Boocock1, Lennart Minthon3, Oskar Hansson3, Amanda Kathleen Miles1, Sabina M Janciauskiene5, Donald Warden4, A. David Smith4, Gordon Wilcock4, Noor Kalsheker2, Robert Rees1, Balwir Matharoo-Ball6, Kevin Morgan2
We have used proteomic fingerprinting to investigate diagnosis of Alzheimer's disease (AD). Samples of lumbar cerebrospinal fluid (CSF) from clinically-diagnosed AD cases (n = 33), age-matched controls (n = 20), and mild cognitive impairment (MCI) patients (n = 10) were used to obtain proteomic profiles, followed by bioinformatic analysis that generated a set of potential biomarkers in CSF samples that could discriminate AD cases from controls. The identity of the biomarker ions was determined using mass spectroscopy. The panel of seven peptide biomarker ions was able to discriminate AD patients from controls with a median accuracy of 95% (sensitivity 85%, specificity 97%). When this model was applied to an independent blind dataset from MCI patients, the intensity of signals was intermediate between the control and AD patients implying that these markers could potentially predict patients with early neurodegenerative disease. The panel were identified, in order of predictive ability, as SPARC-like 1 protein, fibrinogen alpha chain precursor, amyloid-β, apolipoprotein E precursor, serum albumin precursor, keratin type I cytoskeletal 9, and tetranectin. The 7 ion ANN model was further validated using an independent cohort of samples, where the model was able to classify AD cases from controls with median accuracy of 84.5% (sensitivity 93.3%, specificity 75.7%). Validation by immunoassay was performed on the top three identified markers using the discovery samples and an independent sample cohort which was from postmortem confirmed AD patients (n = 17).