阿尔茨海默病患者一般认知、视觉评估皮质萎缩与脑脊液生物标志物的关系：来自中国 PUMCH 队列的一项横断面研究。
Relationship Between General Cognition, Visual Assessed Cortical Atrophy, and Cerebrospinal Fluid Biomarkers in Alzheimer's Disease: A Cross-Sectional Study from a Chinese PUMCH Cohort.
机构信息
Department of Neurology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science/Peking Union Medical College, Beijing, China.
State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China.
出版信息
J Alzheimers Dis. 2021;82(1):205-214. doi: 10.3233/JAD-210344.
BACKGROUND
Cerebrospinal fluid (CSF) biomarkers are widely accepted as manifestations of Alzheimer's disease (AD) pathogenesis and incorporated into biological definition of AD. However, the correlations between CSF and other biomarkers such as neuroimaging and neuropsychiatric evaluation are complicated and inconsistent.
OBJECTIVE
We aimed to better interpreting CSF biomarkers results accompanying with other indexes in improving accurate diagnosis of AD.
METHODS
112 AD patients and 30 cognitive normal controls were selected. Commercial accessible ELISA kits were introduced for measurement of CSF t-tau, p-tau181, Aβ1-42, and NfL based on standard protocol. MRI examinations were performed using a 3-T MRI scanner and visual rating scales including medial temporal atrophy score and Koedam's scale were used to evaluate medial temporal atrophy and posterior region atrophy.
RESULTS
CSF biomarkers' profile including decreased concentration of Aβ1-42, increased concentration of t-tau, p-tau181, t-tau/Aβ 1-42, and NfL were diagnostic between AD and control. CSF biomarkers profile was not influenced by the APOE genotype. Increased concentration of t-tau and NfL, as well as ratio of t-tau/Aβ 1-42 were related to decrease of Mini-Mental State Examination (MMSE) score while concentration of Aβ1-42 not. Visual assessed cortical atrophy was related to MMSE score, but most of the CSF biomarkers were not related to atrophy, except that increased concentration of p-tau181 was significantly associated with atrophy of posterior cortical region.
CONCLUSION
Our results supported CSF biomarkers were helpful in diagnosis of AD. However, CSF biomarkers were cross-sectional reflection of pathogenesis, which did not correlate well with clinical progression. CSF biomarkers should be interpreted in combination with MRI and cognitive evaluation in clinical use.
背景
脑脊液（CSF）生物标志物被广泛认为是阿尔茨海默病（AD）发病机制的表现，并被纳入 AD 的生物学定义。然而，CSF 与神经影像学和神经心理学评估等其他生物标志物之间的相关性复杂且不一致。
目的
我们旨在更好地解释伴随其他指标的 CSF 生物标志物结果，以提高 AD 的准确诊断。
方法
选择 112 例 AD 患者和 30 例认知正常对照者。根据标准方案，采用商业上可获得的 ELISA 试剂盒测量 CSF t-tau、p-tau181、Aβ1-42 和 NfL。使用 3-T MRI 扫描仪进行 MRI 检查，并使用视觉评分量表（包括内侧颞叶萎缩评分和 Koedam 量表）评估内侧颞叶萎缩和后区萎缩。
结果
AD 与对照组之间 CSF 生物标志物特征包括 Aβ1-42 浓度降低、t-tau、p-tau181、t-tau/Aβ1-42 和 NfL 浓度增加。CSF 生物标志物特征不受 APOE 基因型影响。t-tau 和 NfL 浓度增加以及 t-tau/Aβ1-42 比值与 Mini-Mental State Examination（MMSE）评分降低有关，而 Aβ1-42 浓度则无关。视觉评估的皮质萎缩与 MMSE 评分相关，但大多数 CSF 生物标志物与萎缩无关，除了 p-tau181 浓度增加与皮质后区萎缩显著相关。
结论
我们的结果支持 CSF 生物标志物有助于 AD 的诊断。然而，CSF 生物标志物是发病机制的横断面反映，与临床进展相关性不佳。在临床应用中，CSF 生物标志物应与 MRI 和认知评估结合解释。
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