在一个多种族人群样本中，临床阿尔茨海默病的血液生物标志物的纵向变化。
Longitudinal Changes in Blood Biomarkers of Clinical Alzheimer Disease in a Biracial Population Sample.
机构信息
From the Rush Institute for Healthy Aging (K.R., D.E.), Rush University Medical Center, Chicago IL; Stanford University (E.A.M.), Palo Alto, CA; Rush Alzheimer's Disease Center (N.A., L.L.B., R.W.), Chicago IL; Boston University (J.W.), Boston, MA; and Department of Neurology (C.S.D.), University of California, Davis.
出版信息
Neurology. 2023 Feb 21;100(8):e874-e883. doi: 10.1212/WNL.0000000000201289. Epub 2022 Nov 29.
BACKGROUND AND OBJECTIVES
Recent studies suggest the utility of blood biomarkers in detecting changes in neurodegenerative disorders. The objective of our research was to test the hypothesis that the longitudinal changes in total tau (t-tau), neurofilament light chain (Nf-L), and glial fibrillary acidic protein (GFAP) are associated with structural MRI and the development of clinical Alzheimer disease (AD) and cognitive decline.
METHODS
Data came from a population-based sample with serum concentrations of t-tau, Nf-L, and GFAP and cognitive characteristics measured over 17 years. The inclusion criteria for this investigation were based on participants with blood samples, cognitive function testing, and clinical diagnosis for AD. The longitudinal changes in the serum biomarkers were examined using linear mixed models for log10-transformed concentrations.
RESULTS
In 1,327 participants (60% Black participants and 60% women, the concentration of t-tau increased annually by 4.8% (95% CI = 4.0-5.6) and Nf-L by 5.9% (95% CI = 5.4-6.4). The longitudinal change in GFAP was higher among Black participants than among White participants (4.4% vs 3.5% per year, = 0.028). Baseline MRI characteristics were associated with the longitudinal changes in serum biomarkers of clinical AD. Specifically, a higher baseline third ventricular volume was associated with a higher rate of increase in the concentration of t-tau, and white matter hyperintensities predicted a higher rate of increase in Nf-L. The rate of change in concentrations of t-tau, Nf-L, and GFAP was significantly higher among those who developed clinical AD than in those with no cognitive impairment. For each standard deviation unit decline in global cognition, longitudinal change in t-tau increased by 81% (95% CI = 76-86), Nf-L by 113% (95% CI = 105-120), and GFAP by 66% (95% CI = 62-70).
DISCUSSION
Blood biomarkers showed significant longitudinal changes corresponding to cognitive decline, clinical AD, and structural MRI characteristics. Our findings show that longitudinal changes in serum biomarkers were associated with several cognitive endophenotypes.
CLASSIFICATION OF EVIDENCE
The study found Class II evidence that longitudinal changes in serum t-tau, Nf-L, and GFAP were associated with cognitive decline and the development of clinical AD in people older than 65 years.
背景与目的
最近的研究表明，血液生物标志物在检测神经退行性疾病的变化方面具有一定的作用。本研究旨在验证以下假设，即总tau（t-tau）、神经丝轻链（Nf-L）和胶质纤维酸性蛋白（GFAP）的纵向变化与结构磁共振成像（MRI）以及临床阿尔茨海默病（AD）的发展和认知能力下降有关。
方法
数据来自一个基于人群的样本，该样本在 17 年内测量了血清 t-tau、Nf-L 和 GFAP 的浓度以及认知特征。本研究的纳入标准基于有血样、认知功能测试和 AD 临床诊断的参与者。使用线性混合模型对数 10 转换后的浓度来检查血清生物标志物的纵向变化。
结果
在 1327 名参与者中（60%为黑人参与者，60%为女性），t-tau 的浓度每年增加 4.8%（95%置信区间为 4.0-5.6），Nf-L 每年增加 5.9%（95%置信区间为 5.4-6.4）。黑人参与者的 GFAP 纵向变化高于白人参与者（每年分别为 4.4%和 3.5%，P=0.028）。基线 MRI 特征与 AD 临床相关的血清生物标志物的纵向变化有关。具体而言，第三脑室体积越大，t-tau 浓度的增加速度越快，而脑白质高信号与 Nf-L 浓度增加速度加快有关。与无认知障碍者相比，发展为临床 AD 者的 t-tau、Nf-L 和 GFAP 浓度变化率显著更高。全球认知功能每下降一个标准差单位，t-tau 的纵向变化增加 81%（95%置信区间为 76-86），Nf-L 增加 113%（95%置信区间为 105-120），GFAP 增加 66%（95%置信区间为 62-70）。
讨论
血液生物标志物显示出与认知能力下降、临床 AD 和结构 MRI 特征相对应的显著纵向变化。我们的研究结果表明，血清生物标志物的纵向变化与几种认知表型有关。
证据分类
该研究发现 II 级证据表明，65 岁以上人群血清 t-tau、Nf-L 和 GFAP 的纵向变化与认知能力下降和临床 AD 的发展有关。
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