Cheng Zhaozhao, Dai Linbin, Wu Yan, Cao Yuqin, Chai Xianliang, Wang Peng, Liu Chang, Ni Ming, Gao Feng, Wang Qiong, Lv Xinyi
Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Neurodegenerative Disorder Research Center, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Front Neurol. 2023 Feb 16;14:1077860. doi: 10.3389/fneur.2023.1077860. eCollection 2023.
Blood-brain barrier (BBB) damage is considered an important part of Alzheimer's disease (AD) progression, and cerebral small-vessel disease (CSVD) is commonly associated with AD. However, the relationship between BBB damage, small cerebrovascular lesions, especially cerebral microbleeds (CMBs), and amyloid and tau biomarkers remains controversial. Therefore, our study aimed to further investigate their association in our cohort of patients with AD.
A total of 139 individuals were divided into probable AD (F-florbetapir PET positive, = 101) and control group (cognitively normal, = 38). The levels of cerebrospinal fluid (CSF) and plasma t-tau, p-tau181, Aβ40, Aβ42, and albumin were measured using corresponding commercial assay kits, and the CSF/plasma albumin ratio (Qalb), an indicator of BBB dysfunction, was calculated. CSVD burden and the number of CMBs were defined using magnetic resonance imaging.
Patients with AD had higher Qalb ( = 0.0024), higher numbers of CMBs ( = 0.03), and greater CSVD burden ( < 0.0001). In the AD group, CMBs and CSVD correlated with a higher Qalb ( = 0.03), and the numbers of CMBs negatively correlated with CSF Aβ42 ( = 0.02).
Blood-brain barrier damage was accompanied by a more severe burden of CSVD, including CMB, in patients with AD.
血脑屏障（BBB）损伤被认为是阿尔茨海默病（AD）进展的重要组成部分，脑小血管疾病（CSVD）通常与AD相关。然而，BBB损伤、脑小血管病变尤其是脑微出血（CMB）与淀粉样蛋白和tau生物标志物之间的关系仍存在争议。因此，我们的研究旨在进一步调查它们在我们的AD患者队列中的关联。
总共139名个体被分为可能的AD组（氟代贝他吡PET阳性，n = 101）和对照组（认知正常，n = 38）。使用相应的商业检测试剂盒测量脑脊液（CSF）和血浆中的总tau蛋白（t-tau）、磷酸化tau蛋白181（p-tau181）、淀粉样蛋白β40（Aβ40）、淀粉样蛋白β42（Aβ42）和白蛋白水平，并计算CSF/血浆白蛋白比值（Qalb），这是BBB功能障碍的一个指标。使用磁共振成像定义CSVD负担和CMB数量。
AD患者的Qalb更高（P = 0.0024），CMB数量更多（P = 0.03），CSVD负担更重（P < 0.0001）。在AD组中，CMB和CSVD与更高的Qalb相关（P = 0.03），CMB数量与CSF Aβ42呈负相关（P = 0.02）。
AD患者的血脑屏障损伤伴随着包括CMB在内的更严重的CSVD负担。
