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
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
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DOI：
10.3233/jad-210344
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发表时间：
2021-01-01
影响因子：
4
通讯作者：
Gao, Jing
中科院分区：
文献类型：
--
作者：
Mao, Chenhui;Sha, Longze;Gao, Jing
背景资料：脑脊液（CSF）生物标志物被广泛接受为阿尔茨海默病（AD）发病机制的表现，并纳入AD的生物学定义。目的：探讨脑脊液生物标志物与其他指标的相关性，以提高对AD的诊断准确性。方法：选择112例AD患者和30例认知功能正常的对照者。基于标准方案，引入商业可获得的ELISA试剂盒用于测量CSF t-tau、p-tau 181、A β（1-42）和NfL。结果：脑脊液中A β（1-42）浓度降低，t-tau、p-tau 181、t-tau/A β（1 - 42）、NfL浓度升高，可作为AD和对照组的诊断指标。CSF生物标志物谱不受APOE基因型的影响。t-tau、NfL浓度及t-tau/A β（1-42）比值升高与简易精神状态检查（MMSE）评分降低相关，而A β（1-42）浓度升高与MMSE评分降低无关。视觉评估的皮质萎缩与MMSE评分相关，但除p-tau 181浓度升高与后皮质区萎缩显著相关外，大多数CSF生物标志物与萎缩无关。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好。在临床应用中，应结合MRI和认知评估来解释CSF生物标志物。
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, A beta(1-42), and NfL based on standard protocol. MRIexaminations 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 A beta(1-42), increased concentration of t-tau, p-tau181, t-tau/A beta(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/A beta(1-42) were related to decrease of Mini-Mental State Examination (MMSE) score while concentration of A beta(1-42) 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.