Blood-brain barrier leakage in Alzheimer's disease: From discovery to clinical relevance.
Blood-brain barrier leakage in Alzheimer's disease: From discovery to clinical relevance.
复制标题
DOI：
10.1016/j.pharmthera.2022.108119
复制
发表时间：
2022-06
影响因子：
13.5
通讯作者：
Hartz, Anika M. S.
中科院分区：
文献类型：
--
作者：
Nehra, Geetika;Bauer, Bjoern;Hartz, Anika M. S.
关键词：
阿尔茨海默病(AD)是痴呆症最常见的形式。AD脑病理学在临床症状出现前几十年就开始了。早期的病理特征之一是血脑屏障功能障碍，其特征是屏障渗漏，并与认知能力下降有关。在这篇综述中，我们总结了关于AD中屏障渗漏的程度和临床相关性的现有文献。首先，我们关注AD动物模型及其基于年龄和遗传背景对屏障渗漏的易感性。第二，我们在临床和尸检研究中重新检查屏障功能障碍，总结导致患者屏障渗漏的变化，并强调屏障渗漏在AD中的临床相关性。第三，我们总结了将屏障渗漏与AD的神经退行性变和认知功能下降联系起来的信号机制。最后，我们讨论了临床相关性和潜在的治疗策略，并对AD屏障渗漏的研究提供了未来的展望。识别屏障渗漏的机制步骤有可能揭开新的靶点，这些靶点可用于开发新的治疗策略来修复屏障渗漏，减缓AD和AD相关痴呆的认知能力下降。
Alzheimer’s disease (AD) is the most common form of dementia. AD brain pathology starts decades before the onset of clinical symptoms. One early pathological hallmark is blood-brain barrier dysfunction characterized by barrier leakage and associated with cognitive decline. In this review, we summarize the existing literature on the extent and clinical relevance of barrier leakage in AD. First, we focus on AD animal models and their susceptibility to barrier leakage based on age and genetic background. Second, we re-examine barrier dysfunction in clinical and postmortem studies, summarize changes that lead to barrier leakage in patients and highlight the clinical relevance of barrier leakage in AD. Third, we summarize signaling mechanisms that link barrier leakage to neurodegeneration and cognitive decline in AD. Finally, we discuss clinical relevance and potential therapeutic strategies and provide future perspectives on investigating barrier leakage in AD. Identifying mechanistic steps underlying barrier leakage has the potential to unravel new targets that can be used to develop novel therapeutic strategies to repair barrier leakage and slow cognitive decline in AD and AD-related dementias.
登录
查看更多内容
DOI：
10.1523/jneurosci.1064-09.2009
发表时间：
2009-10-14
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Abdul HM;Sama MA;Furman JL;Mathis DM;Beckett TL;Weidner AM;Patel ES;Baig I;Murphy MP;LeVine H 3rd;Kraner SD;Norris CM
通讯作者：
Norris CM
影响因子：
5
作者：
Batarseh YS;Bharate SS;Kumar V;Kumar A;Vishwakarma RA;Bharate SB;Kaddoumi A
通讯作者：
Kaddoumi A
DOI：
10.1016/s0169-328x(98)00066-7
发表时间：
1998-06-01
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Bales, KR;Du, YS;Paul, SM
通讯作者：
Paul, SM
影响因子：
2.5
作者：
AKIYAMA, H;IKEDA, K;MCGEER, PL
通讯作者：
MCGEER, PL
影响因子：
4
作者：
Al Rihani, Sweilem B.;Lan, Renny S.;Kaddoumi, Amal
通讯作者：
Kaddoumi, Amal