Neurology:阿尔茨海默病新标志物VILIP-1可能预测心智能力下降

2012-03-09 MedSci MedSci原创

3月6日,《神经病学》(Neurology)杂志上的一项研究论文称,圣路易斯华盛顿大学医学院的研究人员发现阿尔茨海默病的一个新标志物可预测患者确诊后的记忆力及其他心智能力下降的速度。 在60例早期阿尔茨海默病患者中,脊髓液中较高水平的标志物(视锥蛋白样蛋白1(VILIP-1))与随后数年较快的心智能力下降相关。 科学家需要在更大规模的研究中证实该结果,但新数据表明, VILIP-1可能成为预测

3月6日,《神经病学》(Neurology)杂志上的一项研究论文称,圣路易斯华盛顿大学医学院的研究人员发现阿尔茨海默病的一个新标志物可预测患者确诊后的记忆力及其他心智能力下降的速度。

在60例早期阿尔茨海默病患者中,脊髓液中较高水平的标志物(视锥蛋白样蛋白1(VILIP-1))与随后数年较快的心智能力下降相关。

科学家需要在更大规模的研究中证实该结果,但新数据表明, VILIP-1可能成为预测阿尔茨海默病进展的更好(优于其它标志物)指标。

“VILIP-1可能是脑细胞进展性损伤(阿尔茨海默病引起)的强有力预测指标,”本文的主要作者Rawan Tarawneh博士(如今为约旦大学神经病学助理教授)说。“这对预测病程及临床试验中评价新的治疗方法非常有用。”

VILIP-1最初于实验室(Jack Ladenson博士, Oree M. Carroll与Lillian B. Ladenson (华盛顿大学病理学与免疫学系临床化学教授))中被确定为脑细胞损伤的潜在指标。科学家们认为VILIP-1作为脑细胞中的钙传感器。细胞受损时其释放到脑脊液中。

Tarawneh是该实验室(David Holtzman博士, Andrew B.与Gretchen P. Jones 教授)的前博士后助理研究员及华盛顿大学的神经病学系主任。在早期的一项研究中,她及其同事发现:含有高水平VILIP-1的正常受试者更可能于2-3年的随访期间发生认知障碍与阿尔茨海默病。

科学家们于华盛顿大学医学院Charles F.与Joanne Knight阿尔茨海默病研究中心鉴定出非常轻微或轻度阿尔茨海默病患者进行该新研究。首先,研究人员检测了患者脑脊髓液中的VILIP-1水平,并使用大量测试评估其心智能力。每年重复认知功能测试。

“记忆力及其它心理能力在含最高水平VILIP-1的患者中下降速度较快,”Tarawneh说。“在有阿尔茨海默病早期症状的患者中,VILIP-1似乎与本研究中使用的其它预后指标一样好,可能甚至优于后者。”

研究的2个其它指标为淀粉样β蛋白与tau蛋白。脊髓液中这些蛋白水平的变化主要反映下列事实:淀粉样β蛋白与tau蛋白开始在大脑中形成异常沉积。相比之下,VILIP-1可能显示由阿尔茨海默病引起的脑部变化中脑细胞的损害程度有多大。

“这些结果耐人寻味,但我们需要一个更大规模的研究以充分了解与其它标志物相比,VILIP-1的预测机制,”Tarawneh说。

她正与华盛顿大学的科学家一起对广泛用于研究的VILIP-1检测试验进行标准化。

本研究受美国国立卫生研究院(NIH)、西门子医疗保健诊断和Charles与Joanne Knight阿兹海默氏症研究机构资助。

doi:10.1212/WNL.0b013e318248e568
CSF VILIP-1 predicts rates of cognitive decline in early Alzheimer disease.

Tarawneh R, Lee JM, Ladenson JH, Morris JC, Holtzman DM.

Abstract: OBJECTIVE:Measures of neuronal damage/dysfunction are likely good surrogates for disease progression in Alzheimer disease (AD). CSF markers of neuronal injury may offer utility in predicting disease progression and guiding prognostic and outcome assessments in therapeutic trials. Visinin-like protei... OBJECTIVE:Measures of neuronal damage/dysfunction are likely good surrogates for disease progression in Alzheimer disease (AD). CSF markers of neuronal injury may offer utTarawneh R, Lee JM, Ladenson JH, Morris JC, Holtzman DM.
ility in predicting disease progression and guiding prognostic and outcome assessments in therapeutic trials. Visinin-like protein-1 (VILIP-1) has demonstrated potential utility as a marker of neuronal injury. We here investigate the utility of VILIP-1 and VILIP-1/Aβ42 in predicting rates of cognitive decline in early AD.
METHODS:Individuals with a clinical diagnosis of very mild or mild AD (n = 60) and baseline CSF measures of VILIP-1, tau, p-tau181, and Aβ42 were followed longitudinally for an average of 2.6 years. Annual assessments included the Clinical Dementia Rating (CDR), CDR-sum of boxes (CDR-SB), and global composite scores. Mixed linear models assessed the ability of CSF biomarker measures to predict rates of cognitive decline over time.
RESULTS:Baseline CSF VILIP-1 and VILIP-1/Aβ42 levels predicted rates of future decline in CDR-SB and global composite scores over the follow-up period. Individuals with CSF VILIP-1 ≥560 pg/mL (corresponding to the upper tercile) progressed much more rapidly in CDR-SB (1.61 boxes/year; p = 0.0077) and global scores (-0.53 points/year; p = 0.0002) than individuals with lower values (0.85 boxes/year and -0.15 points/year, respectively) over the follow-up period. CSF tau, p-tau181, tau/Aβ42, and p-tau181/Aβ42 also predicted more rapid cognitive decline in CDR-SB and global scores over time.
CONCLUSION:These findings suggest that CSF VILIP-1 and VILIP-1/Aβ42 predict rates of global cognitive decline similarly to tau and tau/Aβ42, and may be useful CSF surrogates for neurodegeneration in early AD.

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    2013-02-14 yinhl1978
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