神经退行性变、突触完整性和星形胶质细胞激活的脑脊液生物标志物在整个临床阿尔茨海默病谱中。
Cerebrospinal fluid biomarkers of neurodegeneration, synaptic integrity, and astroglial activation across the clinical Alzheimer's disease spectrum.
机构信息
Alzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands.
Alzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands.
出版信息
Alzheimers Dement. 2019 May;15(5):644-654. doi: 10.1016/j.jalz.2019.01.004. Epub 2019 Mar 8.
INTRODUCTION
We investigated relations between amyloid-β (Aβ) status, apolipoprotein E (APOE) ε4, and cognition, with cerebrospinal fluid markers of neurogranin (Ng), neurofilament light (NFL), YKL-40, and total tau (T-tau).
METHODS
We included 770 individuals with normal cognition, mild cognitive impairment, and Alzheimer's disease (AD)-type dementia from the EMIF-AD Multimodal Biomarker Discovery study. We tested the association of Ng, NFL, YKL-40, and T-tau with Aβ status (Aβ- vs. Aβ+), clinical diagnosis APOE ε4 carriership, baseline cognition, and change in cognition.
RESULTS
Ng and T-tau distinguished between Aβ+ from Aβ- individuals in each clinical group, whereas NFL and YKL-40 were associated with Aβ+ in nondemented individuals only. APOE ε4 carriership did not influence NFL, Ng, and YKL-40 in Aβ+ individuals. NFL was the best predictor of cognitive decline in Aβ+ individuals across the cognitive spectrum.
DISCUSSION
Axonal degeneration, synaptic dysfunction, astroglial activation, and altered tau metabolism are involved already in preclinical AD. NFL may be a useful prognostic marker.
简介
我们研究了淀粉样蛋白-β（Aβ）状态、载脂蛋白 E（APOE）ε4 与认知之间的关系，以及神经颗粒蛋白（Ng）、神经丝轻链（NFL）、YKL-40 和总 tau（T-tau）等脑脊液标志物。
方法
我们纳入了来自 EMIF-AD 多模态生物标志物发现研究的 770 名认知正常、轻度认知障碍和阿尔茨海默病（AD）型痴呆患者。我们测试了 Ng、NFL、YKL-40 和 T-tau 与 Aβ 状态（Aβ+与 Aβ-）、临床诊断 APOE ε4 携带情况、基线认知以及认知变化的相关性。
结果
Ng 和 T-tau 在每个临床组中均能区分 Aβ+与 Aβ-个体，而 NFL 和 YKL-40 仅与非痴呆个体的 Aβ+相关。APOE ε4 携带情况并未影响 Aβ+个体中的 NFL、Ng 和 YKL-40。在认知谱上，NFL 是 Aβ+个体认知下降的最佳预测因子。
讨论
轴突变性、突触功能障碍、星形胶质细胞激活和 tau 代谢改变已涉及到临床前 AD。NFL 可能是一种有用的预后标志物。
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