CSF tau/Aβ42 ratio for increased risk of mild cognitive impairment -: A follow-up study
CSF tau/Aβ42 ratio for increased risk of mild cognitive impairment -: A follow-up study
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DOI：
10.1212/01.wnl.0000267428.62582.aa
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发表时间：
2007-08-14
期刊：
影响因子：
9.9
通讯作者：
Montine, T. J.
中科院分区：
文献类型：
--
作者：
Li, G.;Sokal, I.;Montine, T. J.
背景：阿尔茨海默病（AD）的过程可能在认知障碍（潜伏性AD）发病前几年开始，经过轻度认知障碍（MCI）的前驱期，最终发展为痴呆。虽然许多研究已经评估了脑脊液tau和A β(42)作为阿尔茨海默病痴呆或前驱阶段的生物标志物，但我们还没有任何研究评估这些潜在的阿尔茨海默病脑脊液生物标志物。方法：我们使用Luminex试剂测定了129名年龄从21岁到100岁的对照个体的脑脊液tau/A β (T/A β)的比率（42）；为了进行比较，我们纳入了MCI （n = 12）、可能的AD （n = 21）或其他神经退行性疾病（n = 12）的患者。结果：我们发现16%的对照组患者CSF T/A β异常升高；所有人的年龄都在53岁以上。使用与年龄匹配的CSF T/A β正常的对照组，我们发现高CSF T/A β亚组的对照组载脂蛋白E基因的epsilon 4等位基因的频率显著增加，并且在长达42个月的随访期间显著增加了转化为MCI的风险，这表明他们在腰椎穿刺时患有潜在的AD。结论：这些普遍适用的方法建立了临界值，以识别转化为轻度认知障碍风险增加的对照个体，这可能有助于人们权衡新的预防治疗的风险-收益比，并有助于研究人员努力丰富潜伏性阿尔茨海默病患者的临床试验人群。
Background: Processes of Alzheimer disease (AD) likely begin years prior to the onset of cognitive impairment (latent AD), progress though a prodromal phase of mild cognitive impairment (MCI), and culminate in dementia. While many studies have evaluated CSF tau and A beta(42) as biomarkers of the dementia or prodromal stages of AD, we are unaware of any study to evaluate these potential CSF biomarkers of latent AD.Methods: We determined the ratio of CSF tau/A beta(42) (T/A beta) using Luminex reagents in 129 control individuals that spanned from 21 to 100 years of age; for comparison we included patients with MCI (n = 12), probable AD (n = 21), or other neurodegenerative diseases (n = 12).Results: We identified 16% of the control group with abnormally elevated CSF T/A beta; all were 53 years or older. Using age-matched controls with normal CSF T/A beta we showed that the high CSF T/A beta subgroup of controls had significantly increased frequency of the epsilon 4 allele of the apolipoprotein E gene and significantly increased risk of conversion to MCI during follow-up of up to 42 months suggesting that they had latent AD at the time of lumbar puncture.Conclusions: These generally applicable methods establish cutoff values to identify control individuals at increased risk of conversion to mild cognitive impairment which may be useful to people weighing the risk-benefit ratio of new preventive therapeutics and to researchers striving to enrich clinical trial populations with people with latent Alzheimer disease.