Cerebrospinal fluid tau/β-amyloid42 ratio as a prediction of cognitive decline in nondemented older adults
Cerebrospinal fluid tau/β-amyloid42 ratio as a prediction of cognitive decline in nondemented older adults
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DOI：
10.1001/archneur.64.3.noc60123
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发表时间：
2007-03-01
影响因子：
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通讯作者：
Holtzman, David M.
中科院分区：
文献类型：
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作者：
Fagan, Anne M.;Roe, Catherine M.;Holtzman, David M.
目的：研究脑脊液(CSF)和血浆指标区分早期阿尔茨海默病(AD)(由临床标准和脑淀粉样蛋白的存在/不存在定义)与非痴呆衰老的能力，并评估这些生物标志物是否可以预测认知正常个体未来的痴呆。设计：评估脑脊液β-淀粉样蛋白(40)(Aβ(40))，Aβ(42)，tau，磷酸化tau(181)，和血浆Aβ(40)和Aβ(42)和纵向临床随访(1到8年)。背景：通过AD研究中心进行的健康老龄化和痴呆的纵向研究。参与者：社区居住的志愿者(n=139)，年龄60到91岁，临床判断为认知正常(临床痴呆评分[CDR]，0)或非常轻度(CDR，0.5)或轻度(CDR，1)AD痴呆。结果：非常轻度或轻度AD患者的脑脊液Aβ平均水平降低(42例)，而脑脊液tau和磷酸化tau水平升高(181例)。脑脊液Aβ(42)水平与痴呆和非痴呆患者脑淀粉样蛋白(匹兹堡化合物B成像)的存在或不存在完全一致。脑脊液tau/Aβ(42)比值(调整后危险比5.21；95%可信区间1.58-17.22)和磷酸化tau(181)/Aβ(42)比值(调整后危险比4.39；95%可信区间1.62-11.86)预测CDR由0转为CDR>0。结论：最轻微的AD症状期表现出与较晚期AD相同的脑脊液生物标志物表型。此外，当脑脊液Aβ(42)水平与淀粉样蛋白成像相结合时，可增强临床方法，以确定大脑淀粉样蛋白沉积的个体是否存在痴呆症。重要的是，脑脊液tau/Aβ(42)比值作为预测认知正常老年人未来痴呆的先期(临床前)生物标志物显示出很强的前景。
Objectives: To investigate the ability of cerebrospinal fluid (CSF) and plasma measures to discriminate early-stage Alzheimer disease (AD) (defined by clinical criteria and presence/absence of brain amyloid) from nondemented aging and to assess whether these biomarkers can predict future dementia in cognitively normal individuals.Design: Evaluation of CSF beta-amyloid(40) (A beta(40)), A beta(42), tau, phosphorylated tau(181), and plasma A beta(40) and A beta(42) and longitudinal clinical follow-up (from 1 to 8 years).Setting: Longitudinal studies of healthy aging and dementia through an AD research center.Participants: Community-dwelling volunteers (n = 139) aged 60 to 91 years and clinically judged as cognitively normal (Clinical Dementia Rating [CDR], 0) or having very mild (CDR, 0.5) or mild (CDR, 1) AD dementia.Results: Individuals with very mild or mild AD have reduced mean levels of CSF A beta(42) and increased levels of CSF tau and phosphorylated tau(181). Cerebrospinal fluid A beta(42) level completely corresponds with the presence or absence of brain amyloid (imaged with Pittsburgh Compound B) in demented and nondemented individuals. The CSF tau/A beta(42) ratio (adjusted hazard ratio, 5.21; 95% confidence interval, 1.58-17.22) and phosphorylated tau(181)/A beta(42) ratio (adjusted hazard ratio, 4.39; 95% confidence interval, 1.62-11.86) predict conversion from a CDR of 0 to a CDR greater than 0.Conclusions: The very mildest symptomatic stage of AD exhibits the same CSF biomarker phenotype as more advanced AD. In addition, levels of CSF A beta(42), when combined with amyloid imaging, augment clinical methods for identifying in individuals with brain amyloid deposits whether dementia is present or not. Importantly, CSF tau/A beta(42) ratios show strong promise as antecedent (preclinical) biomarkers that predict future dementia in cognitively normal older adults.