Kester Maartje I, Teunissen Charlotte E, Sutphen Courtney, Herries Elizabeth M, Ladenson Jack H, Xiong Chengjie, Scheltens Philip, van der Flier Wiesje M, Morris John C, Holtzman David M, Fagan Anne M
Alzheimer Center and Department of Neurology, VU University Medical Center, PO box 7057, 1007 MB, Amsterdam, The Netherlands.
Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands.
Alzheimers Res Ther. 2015 Sep 17;7(1):59. doi: 10.1186/s13195-015-0142-1.
We examined the utility of cerebrospinal fluid (CSF) proteins, Chitinase-3-like protein 1 (CHI3L1 or YKL-40), a putative marker of inflammation, and Visinin-like protein-1 (VILIP-1), a marker for neuronal injury, for diagnostic classification and monitoring of disease progression in a memory clinic cohort.
CSF levels of YKL-40 and VILIP-1 were measured in 37 cognitively normal, 61 Mild Cognitive Impairment (MCI) and 65 Alzheimer's disease (AD) patients from the memory clinic-based Amsterdam Dementia Cohort who underwent two lumbar punctures, with minimum interval of 6 months and a mean (SE) interval of 2.0(0.1) years. Mean(SE) cognitive follow-up was 3.8 (0.2) years. ANOVA was used to compare baseline differences of log-transformed CSF measures. Cox proportional hazard models were used to evaluate disease progression as a function of CSF tertiles. Linear mixed models were used to evaluate longitudinal change over time. All analyses were sex and age adjusted.
Baseline levels of YKL-40, but not VILIP-1, were higher in MCI and AD patients compared to cognitively normal individuals (mean (SE) pg/mL, 304 (16) and 288 (12) vs. 231 (16), p = 0.03 and p = 0.006). Baseline levels of both YKL-40 and VILIP-1 in MCI predicted progression to AD (HR 95% CI = 3.0 (1.1-7.9) and 4.4 (1.5-13.0), respectively, for highest vs. lowest tertile). YKL-40 increased longitudinally in patients with MCI and AD (mean (SE) pg/mL per year, 8.9 (3.0) and 7.1 (3.1), respectively), but not in cognitively normal individuals, whereas levels of VILIP-1 increased only in MCI (mean (SE), 10.7 (2.6) pg/mL per year).
CSF levels of YKL-40 may have utility for discriminating between cognitively normal individuals and patients with MCI or AD. Increased levels of both YKL-40 and VILIP-1 may be associated with disease progression. These CSF biomarkers should be considered for future evaluation in the characterization of the natural history of AD.
我们研究了脑脊液（CSF）蛋白、几丁质酶-3样蛋白1（CHI3L1或YKL-40，一种假定的炎症标志物）和视锥蛋白样蛋白-1（VILIP-1，一种神经元损伤标志物）在记忆门诊队列中用于疾病诊断分类和病情进展监测的效用。
对来自基于记忆门诊的阿姆斯特丹痴呆队列的37名认知正常者、61名轻度认知障碍（MCI）患者和65名阿尔茨海默病（AD）患者的CSF中YKL-40和VILIP-1水平进行了测量，这些患者均接受了两次腰椎穿刺，间隔至少6个月，平均（标准误）间隔为2.0（0.1）年。平均（标准误）认知随访时间为3.8（0.2）年。采用方差分析比较经对数转换的CSF测量值的基线差异。使用Cox比例风险模型评估疾病进展与CSF三分位数的函数关系。采用线性混合模型评估随时间的纵向变化。所有分析均对性别和年龄进行了校正。
与认知正常个体相比，MCI和AD患者中YKL-40的基线水平较高，而VILIP-1的基线水平无差异（平均（标准误）pg/mL，分别为304（16）和288（12）对比231（16），p = 0.03和p = 0.006）。MCI中YKL-40和VILIP-1的基线水平均预测了向AD的进展（最高三分位数与最低三分位数相比，风险比95%置信区间分别为3.0（1.1 - 7.9）和4.4（1.5 - 13.0））。MCI和AD患者中YKL-40随时间纵向升高（平均（标准误）每年pg/mL，分别为8.9（3.0）和7.1（3.1）），而认知正常个体中未升高，而VILIP-1水平仅在MCI中升高（平均（标准误），每年10.7（2.6）pg/mL）。
CSF中YKL-40水平可能有助于区分认知正常个体与MCI或AD患者。YKL-40和VILIP-1水平升高可能与疾病进展相关。这些CSF生物标志物应在未来AD自然史特征研究中加以考虑用于评估。
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