Cerebrospinal fluid markers for Alzheimer's disease in a cognitively healthy cohort of young and old adults
Cerebrospinal fluid markers for Alzheimer's disease in a cognitively healthy cohort of young and old adults
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DOI：
10.1016/j.jalz.2011.10.003
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发表时间：
2012-11-01
影响因子：
14
通讯作者：
Frisoni, Giovanni B.
中科院分区：
文献类型：
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作者：
Paternico, Donata;Galluzzi, Samantha;Frisoni, Giovanni B.
背景资料：脑脊液（CSF）中低淀粉样蛋白β（42）（A β（42））和高总tau和磷酸化tau（p-tau）浓度是阿尔茨海默病（AD）的生物标志物，反映了淀粉样蛋白斑块和缠结的脑沉积。年龄和载脂蛋白E等位基因E4是AD的两个强有力的危险因素，但很少有数据可用于在正常老化的CSF标记物的影响。目的：研究年龄对认知正常受试者的CSF A β（42）、总tau和p-tau水平的影响。（27%女性，53 +/- 15.3岁，范围：21-88）采用夹心酶联免疫吸附试验测定;其中，分别在61例（75%）和42例（52%）病例中测量总tau和p-tau水平。对全部样本及载脂蛋白E等位基因携带者和非携带者的年龄与脑脊液标志物进行线性回归分析。（= 65岁）受试者（A β（42）：P = .03; tau：P = .02; p-tau：P = .002; tau/A β（42）：P = .004; p-tau/A β（42）：P = .03）。在线性回归模型中证实了标记物水平与年龄的关联，其中观察到总tau蛋白与年龄呈正相关。（B = 2.3; 95%置信区间[CI]：0.89 - 3.7; P = .002），p-tau（B = 0.5; 95% CI：0.1至0.9; P = 0.02）和tau/A β（42）比值（B = 0.006; 95% CI：0.002至0.01; P = 0.002）。没有受试者表现出异常的tau蛋白，而19%表现出异常的CSF A β（42）concentration.Conclusion：在认知正常的受试者中，AD的CSF生物标志物的浓度与年龄相关。进一步的纵向研究可以澄清A β（42）低水平是否代表临床前AD生物标志物。(C)2012年，阿尔茨海默氏症协会。All rights reserved.
Background: Low amyloid beta(42) (A beta(42)) and high total tau and phosphorylated tau (p-tau) concentrations in the cerebrospinal fluid (CSF) are biomarkers of Alzheimer's disease (AD), reflecting brain deposition of amyloid plaques and tangles. Age and apolipoprotein E allele E4 are two strong risk factors for AD, but few data are still available on their effect on CSF markers in normal aging. Objective: To study the effect of age on CSF A beta(42), total tau, and p-tau levels in a well-characterized group of cognitively normal subjects.Methods: CSF A beta(42) levels of 81 subjects (27% female, 53 +/- 15.3 years, range: 21-88) were determined with sandwich enzyme-linked immunosorbent assay; of these, total tau and p-tau levels were measured in 61 (75%) and 42 (52%) cases, respectively. A linear regression analysis between age and CSF markers was carried out on the whole sample and separately in apolipoprotein E allele epsilon 4 carriers and noncarriers.Results: The median levels of all markers were significantly different between young (= 65 years) subjects (A beta(42): P = .03; tau: P = .02; p-tau: P = .002; tau/A beta(42): P = .004; p-tau/A beta(42): P = .03). The association of marker levels with age was confirmed in linear regression models, where a positive relationship with age was observed for total tau (B = 2.3; 95% confidence interval [CI]: 0.89 to 3.7; P = .002), p-tau (B = 0.5; 95% CI: 0.1 to 0.9; P = .02), and tau/A beta(42) ratio (B = 0.006; 95% CI: 0.002 to 0.01; P = .002). No subjects showed abnormal tau, whereas 19% showed abnormal CSF A beta(42) concentrations.Conclusion: In cognitively normal subjects, the concentrations of CSF biomarkers of AD are associated with age. Further longitudinal studies could clarify whether A beta(42) low levels represent a preclinical AD biomarker. (C) 2012 The Alzheimer's Association. All rights reserved.