轻度认知障碍患者脑脊液生物标志物与早期阿尔茨海默病的关联：一项随访研究。

Association between CSF biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment: a follow-up study.

作者信息

Hansson Oskar, Zetterberg Henrik, Buchhave Peder, Londos Elisabet, Blennow Kaj, Minthon Lennart

机构信息

Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Sweden.

出版信息

Lancet Neurol. 2006 Mar;5(3):228-34. doi: 10.1016/S1474-4422(06)70355-6.

DOI:10.1016/S1474-4422(06)70355-6

PMID:16488378

Abstract

BACKGROUND

Disease-modifying treatment strategies for Alzheimer's disease have led to an urgent need for biomarkers to identify the disease at a very early stage. Here, we assess the association between CSF biomarkers and incipient Alzheimer's in patients with mild cognitive impairment (MCI).

METHODS

From a series of 180 consecutive patients with MCI, we assessed 137 who underwent successful lumbar puncture at baseline. Patients at risk of developing dementia were followed clinically for 4-6 years. Additionally, 39 healthy individuals, cognitively stable over 3 years, served as controls. We analysed CSF concentrations of beta amyloid(1-42) (Abeta42), total tau (T-tau), and phosphorylated tau (P-tau181) using Luminex xMAP technology.

FINDINGS

During follow-up, 57 (42%) patients with MCI developed Alzheimer's disease, 21 (15%) developed other forms of dementia, and 56 (41%) remained cognitively stable for 5.2 years (range 4.0-6.8). A combination of CSF T-tau and Abeta42 at baseline yielded a sensitivity of 95% and a specificity of 83% for detection of incipient AD in patients with MCI. The relative risk of progression to Alzheimer's disease was substantially increased in patients with MCI who had pathological concentrations of T-tau and Abeta42 at baseline (hazard ratio 17.7, p<0.0001). The association between pathological CSF and progression to Alzheimer's disease was much stronger than, and independent of, established risk factors including age, sex, education, APOE genotype, and plasma homocysteine. The combination of T-tau and Abeta42/P-tau181 ratio yielded closely similar results (sensitivity 95%, specificity 87%, hazard ratio 19.8).

INTERPRETATION

Concentrations of T-tau, P-tau181, and Abeta42 in CSF are strongly associated with future development of Alzheimer's disease in patients with MCI.

摘要

背景

阿尔茨海默病的疾病修饰治疗策略引发了对在疾病极早期进行识别的生物标志物的迫切需求。在此，我们评估脑脊液生物标志物与轻度认知障碍（MCI）患者早期阿尔茨海默病之间的关联。

方法

在连续的180例MCI患者系列中，我们评估了137例在基线时成功进行腰椎穿刺的患者。有患痴呆症风险的患者接受了4至6年的临床随访。此外，39名认知稳定超过3年的健康个体作为对照。我们使用Luminex xMAP技术分析脑脊液中β淀粉样蛋白（1-42）（Aβ42）、总tau蛋白（T-tau）和磷酸化tau蛋白（P-tau181）的浓度。

研究结果

在随访期间，57例（42%）MCI患者发展为阿尔茨海默病，21例（15%）发展为其他形式的痴呆，56例（41%）在5.2年（范围4.0 - 6.8年）内保持认知稳定。基线时脑脊液T-tau和Aβ42的组合对检测MCI患者早期阿尔茨海默病的敏感性为95%，特异性为83%。基线时T-tau和Aβ42浓度异常的MCI患者进展为阿尔茨海默病的相对风险大幅增加（风险比17.7，p<0.0001）。病理性脑脊液与进展为阿尔茨海默病之间的关联比包括年龄、性别、教育程度、APOE基因型和血浆同型半胱氨酸在内的既定风险因素更强且独立。T-tau与Aβ42/P-tau181比值的组合产生了非常相似的结果（敏感性95%，特异性87%，风险比19.8）。