Gan Jinghuan, Yang Xia, Zhang Guili, Li Xudong, Liu Shuai, Zhang Wei, Ji Yong
Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Department of Cognitive Disorder, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Front Aging Neurosci. 2023 May 4;15:1088140. doi: 10.3389/fnagi.2023.1088140. eCollection 2023.
Blood brain barrier (BBB) breakdown is considered a potential mechanism of dementia. The Alzheimer's disease (AD) biomarkers and vascular factors are also associated with BBB permeability.
In the present study, the combination effects of neuropathological biomarkers of AD and chronic vascular risk factors for BBB were investigated.
The cerebrospinal fluid (CSF)/serum albumin ratio (Qalb), an indicator of BBB permeability, was measured in a total of 95 hospitalized dementia patients. The demographics, clinical information, and laboratory tests were collected from the inpatient records. The CSF neuropathological biomarkers of AD and apolipoprotein E (APOE) genotype were also collected. The mediation analysis model was used to calculate the associations among neuropathological biomarkers of AD (mediator), the Qalb, and chronic vascular risk factors.
Three types of dementia, AD ( = 52), Lewy body dementia (LBD, = 19), and frontotemporal lobar degeneration ( = 24), were included with a mean Qalb of 7.18 (± 4.36). The Qalb was significantly higher in dementia patients with type 2 diabetes mellitus (T2DM, = 0.004) but did not differ based on the presence of APOE ε4 allele, CMBs, or amyloid/tau/neurodegeneration (ATN) framework. The Qalb was negatively associated with the levels of Aβ1-42 (B = -20.775, = 0.009) and Aβ1-40 (B = -305.417, = 0.005) and positively associated with the presence of T2DM (B = 3.382, < 0.001) and the levels of glycosylated hemoglobin (GHb, B = 1.163, < 0.001) and fasting blood glucose (FBG, B = 1.443, < 0.001). GHb is a direct chronic vascular risk factor for higher Qalb (total effect B = 1.135, 95% CI: 0.611-1.659, < 0.001). Ratios of Aβ1-42/Aβ1-40 or t-tau/Aβ1-42 were mediators of the association between the Qalb and GHb; the direct effect of GHb on the Qalb was 1.178 (95% CI: 0.662-1.694, < 0.001).
Glucose exposure can directly or indirectly affect BBB integrity through Aβ and tau, indicating glucose affects BBB breakdown and glucose stability plays an important role in dementia protection and management.
血脑屏障（BBB）破坏被认为是痴呆症的一种潜在机制。阿尔茨海默病（AD）生物标志物和血管因素也与BBB通透性相关。
在本研究中，调查了AD神经病理学标志物与BBB慢性血管危险因素的联合作用。
对总共95名住院痴呆患者测量了脑脊液（CSF）/血清白蛋白比率（Qalb），这是BBB通透性的一个指标。从住院记录中收集人口统计学、临床信息和实验室检查结果。还收集了AD的CSF神经病理学标志物和载脂蛋白E（APOE）基因型。使用中介分析模型来计算AD神经病理学标志物（中介变量）、Qalb和慢性血管危险因素之间的关联。
纳入了三种类型的痴呆症，即AD（n = 52）、路易体痴呆（LBD，n = 19）和额颞叶变性（n = 24），平均Qalb为7.18（±4.36）。2型糖尿病（T2DM）痴呆患者的Qalb显著更高（P = 0.004），但基于APOE ε4等位基因、脑微出血（CMBs）或淀粉样蛋白/ tau /神经变性（ATN）框架的存在情况并无差异。Qalb与Aβ1 - 42水平呈负相关（B = -20.775，P = 0.009）和Aβ1 - 40水平呈负相关（B = -305.417，P = 0.005），与T2DM的存在呈正相关（B = 3.382，P < 0.001）以及与糖化血红蛋白（GHb，B = 1.163，P < 0.001）和空腹血糖（FBG，B = 1.443，P < 0.001）水平呈正相关。GHb是导致Qalb升高的直接慢性血管危险因素（总效应B = 1.135，95%CI：0.611 - 1.659，P < 0.001）。Aβ1 - 42/Aβ1 - 40或t - tau/Aβ1 - 42比率是Qalb与GHb之间关联的中介变量；GHb对Qalb的直接效应为1.178（95%CI：0.662 - 1.694，P < 0.001）。
葡萄糖暴露可通过Aβ和tau直接或间接影响BBB完整性，表明葡萄糖影响BBB破坏，且葡萄糖稳定性在痴呆症的预防和管理中起重要作用。
