Blood–brain barrier breakdown in dementia with Lewy bodies

IF 5.9 1区医学 Q1 NEUROSCIENCES

Fluids and Barriers of the CNS Pub Date : 2024-09-17 DOI:10.1186/s12987-024-00575-z

Jinghuan Gan, Ziming Xu, Zhichao Chen, Shuai Liu, Hao Lu, Yajie Wang, Hao Wu, Zhihong Shi, Huijun Chen, Yong Ji

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Abstract

Blood–brain barrier (BBB) dysfunction has been viewed as a potential underlying mechanism of neurodegenerative disorders, possibly involved in the pathogenesis and progression of Alzheimer’s disease (AD). However, a relation between BBB dysfunction and dementia with Lewy bodies (DLB) has yet to be systematically investigated. Given the overlapping clinical features and neuropathology of AD and DLB, we sought to evaluate BBB permeability in the context of DLB and determine its association with plasma amyloid-β (Aβ) using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). For this prospective study, we examined healthy controls (n = 24, HC group) and patients diagnosed with AD (n = 29) or DLB (n = 20) between December 2020 and April 2022. Based on DCE-MRI studies, mean rates of contrast agent transfer from intra- to extravascular spaces (Ktrans) were calculated within regions of interest. Spearman’s correlation and multivariate linear regression were applied to analyze associations between Ktrans and specific clinical characteristics. In members of the DLB (vs HC) group, Ktrans values of cerebral cortex (p = 0.024), parietal lobe (p = 0.007), and occipital lobe (p = 0.014) were significantly higher; and Ktrans values of cerebral cortex (p = 0.041) and occipital lobe (p = 0.018) in the DLB group were significantly increased, relative to those of the AD group. All participants also showed increased Ktrans values of parietal ( $$\upbeta$$ = 0.391; p = 0.001) and occipital ( $$\upbeta$$ = 0.357; p = 0.002) lobes that were significantly associated with higher scores of the Clinical Dementia Rating, once adjusted for age and sex. Similarly, increased Ktrans values of cerebral cortex ( $$\upbeta$$ = 0.285; p = 0.015), frontal lobe ( $$\upbeta$$ = 0.237; p = 0.043), and parietal lobe ( $$\upbeta$$ = 0.265; p = 0.024) were significantly linked to higher plasma Aβ1-42/Aβ1-40 ratios, after above adjustments. BBB leakage is a common feature of DLB and possibly is even more severe than in the setting of AD for certain regions of the brain. BBB leakage appears to correlate with plasma Aβ1-42/Aβ1-40 ratio and dementia severity.

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路易体痴呆症的血脑屏障破坏

血脑屏障（BBB）功能障碍一直被视为神经退行性疾病的潜在潜在机制，可能与阿尔茨海默病（AD）的发病机制和进展有关。然而，血脑屏障功能障碍与路易体痴呆（DLB）之间的关系还有待系统研究。鉴于AD和DLB的临床特征和神经病理学有重叠之处，我们试图评估DLB的BBB通透性，并使用动态对比增强磁共振成像（DCE-MRI）确定其与血浆淀粉样蛋白-β（Aβ）的关系。在这项前瞻性研究中，我们对2020年12月至2022年4月期间的健康对照组（24人，HC组）和确诊为AD（29人）或DLB（20人）的患者进行了检查。基于 DCE-MRI 研究，我们计算了相关区域内造影剂从血管内向血管外转移的平均速率（Ktrans）。斯皮尔曼相关性和多变量线性回归用于分析 Ktrans 与特定临床特征之间的关联。在DLB（vs HC）组中，大脑皮层（p = 0.024）、顶叶（p = 0.007）和枕叶（p = 0.014）的Ktrans值显著高于AD组；而在DLB组中，大脑皮层（p = 0.041）和枕叶（p = 0.018）的Ktrans值显著高于AD组。所有参与者的顶叶（$$\upbeta$$ = 0.391; p = 0.001）和枕叶（$$\upbeta$$ = 0.357; p = 0.002）的Ktrans值也显示出增加，在对年龄和性别进行调整后，这与临床痴呆评级的较高分数显著相关。同样，经上述调整后，大脑皮层（$$\upbeta$$ = 0.285; p = 0.015）、额叶（$$\upbeta$$ = 0.237; p = 0.043）和顶叶（$$\upbeta$$ = 0.265; p = 0.024）的Ktrans值增加与血浆Aβ1-42/Aβ1-40比率升高有显著联系。BBB 渗漏是 DLB 的常见特征，在大脑的某些区域可能比 AD 更为严重。BBB 渗漏似乎与血浆 Aβ1-42/Aβ1-40 比率和痴呆症严重程度相关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Fluids and Barriers of the CNS Neuroscience-Developmental Neuroscience

CiteScore

10.70

自引率

8.20%

发文量

审稿时长

14 weeks

期刊介绍： "Fluids and Barriers of the CNS" is a scholarly open access journal that specializes in the intricate world of the central nervous system's fluids and barriers, which are pivotal for the health and well-being of the human body. This journal is a peer-reviewed platform that welcomes research manuscripts exploring the full spectrum of CNS fluids and barriers, with a particular focus on their roles in both health and disease. At the heart of this journal's interest is the cerebrospinal fluid (CSF), a vital fluid that circulates within the brain and spinal cord, playing a multifaceted role in the normal functioning of the brain and in various neurological conditions. The journal delves into the composition, circulation, and absorption of CSF, as well as its relationship with the parenchymal interstitial fluid and the neurovascular unit at the blood-brain barrier (BBB).