Increased CSF levels of total Tau in patients with subcortical cerebrovascular pathology and cognitive impairment

ABSTRACT. Cognitive impairment includes mild cognitive decline and dementia, such as Alzheimer's disease (AD) and cerebrovascular-related pathologies. Objective: To investigate the profile of AD-related CSF biomarkers in a sample of cognitively impaired and unimpaired older adults with concomitant subcortical cerebrovascular burden. Methods: Seventy-eight older adults attending an outpatient psychogeriatric clinic were enrolled. Diagnoses were based on clinical, neuropsychological, laboratory, and neuroimaging data. Participants were classified into: cognitively normal (controls, n = 30), mild cognitive impairment (MCI, n = 34), and dementia (AD, n = 14). All subjects were submitted to CSF analyses for determination of amyloid-beta (Aβ1-42), total tau (t-tau), phosphorylated tau (p-tau) and Aβ1-42/p-tau ratio according to the Luminex method. MRI was performed in all individuals, and was scored independently by two experts according to Fazekas scale. Statistical analyses were conducted with the aid of general linear model procedures, and the Chi-squared test. Results: T-tau levels were significantly associated with subcortical lesion pattern when Fazekas was considered as a group factor. CSF biomarkers were not associated with MCI, AD, or controls when considered separately. There was a tendency for reduction in CSF Aβ1-42 together with increasing Fazekas scores, but without statistical significance. Comparisons of Aβ1-42 and t-tau with each clinical group or with each neuroimaging pattern did not reach statistical differences. Likewise, Fazekas scores had no impact on CAMCOG scores. Conclusion: We found a significant association between t-tau levels and subcortical lesions when all Fazekas classifications were considered as a single group; comparisons of Fazekas subgroups and CSF biomarkers did not reach significance.

摘要。认知障碍包括轻度认知下降与痴呆，如阿尔茨海默病（Alzheimer's disease, AD）及脑血管相关病理。研究目的：探究伴皮层下脑血管负荷的认知受损与未受损老年群体中，AD相关脑脊液（Cerebrospinal fluid, CSF）生物标志物的特征。研究方法：纳入78名就诊于老年精神科门诊的老年受试者。诊断依据临床、神经心理学、实验室及神经影像学数据确定。将受试者分为三组：认知正常组（对照组，n=30）、轻度认知障碍组（Mild Cognitive Impairment, MCI，n=34）以及痴呆组（AD组，n=14）。所有受试者均采用Luminex法完成脑脊液分析，以检测淀粉样蛋白β（Amyloid-beta, Aβ1-42）、总tau蛋白（total tau, t-tau）、磷酸化tau蛋白（phosphorylated tau, p-tau）及Aβ1-42/p-tau比值。所有受试者均接受磁共振成像（Magnetic Resonance Imaging, MRI）检查，并由两名专家依据Fazekas量表独立评分。统计分析借助一般线性模型程序与卡方检验完成。研究结果：当将Fazekas评分作为分组因素时，总tau蛋白水平与皮层下病变模式显著相关。单独分析时，脑脊液生物标志物与轻度认知障碍、AD或对照组均无显著关联。脑脊液Aβ1-42水平有随Fazekas评分升高而降低的趋势，但未达到统计学显著性。对比各临床组的Aβ1-42与t-tau水平，或对比各神经影像学亚型的该类指标，均未出现统计学差异。同样，Fazekas评分对CAMCOG评分无显著影响。研究结论：当将所有Fazekas分类视为单个组别时，本研究发现总tau蛋白水平与皮层下病变存在显著关联；但Fazekas亚组与脑脊液生物标志物的对比未达到统计学显著性。