Barisano Giuseppe, Montagne Axel, Kisler Kassandra, Schneider Julie A, Wardlaw Joanna M, Zlokovic Berislav V
Department of Physiology and Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Neuroscience Graduate Program, University of Southern California, Los Angeles, CA, USA.
Nat Cardiovasc Res. 2022 Feb;1(2):108-115. doi: 10.1038/s44161-021-00014-4. Epub 2022 Feb 7.
Vascular dysfunction is frequently seen in disorders associated with cognitive impairment, dementia and Alzheimer's disease (AD). Recent advances in neuroimaging and fluid biomarkers suggest that vascular dysfunction is not an innocent bystander only accompanying neuronal dysfunction. Loss of cerebrovascular integrity, often referred to as breakdown in the blood-brain barrier (BBB), has recently shown to be an early biomarker of human cognitive dysfunction and possibly underlying mechanism of age-related cognitive decline. Damage to the BBB may initiate or further invoke a range of tissue injuries causing synaptic and neuronal dysfunction and cognitive impairment that may contribute to AD. Therefore, better understanding of how vascular dysfunction caused by BBB breakdown interacts with amyloid-β and tau AD biomarkers to confer cognitive impairment may lead to new ways of thinking about pathogenesis, and possibly treatment and prevention of early cognitive impairment, dementia and AD, for which we still do not have effective therapies.
血管功能障碍常见于与认知障碍、痴呆和阿尔茨海默病(AD)相关的疾病中。神经影像学和体液生物标志物的最新进展表明,血管功能障碍并非仅仅是伴随神经元功能障碍的无辜旁观者。脑血管完整性的丧失,通常被称为血脑屏障(BBB)的破坏,最近已被证明是人类认知功能障碍的早期生物标志物,也是年龄相关性认知衰退的潜在机制。血脑屏障的损伤可能引发或进一步引发一系列组织损伤,导致突触和神经元功能障碍以及认知障碍,这可能会导致AD。因此,更好地理解血脑屏障破坏引起的血管功能障碍如何与淀粉样蛋白-β和tau AD生物标志物相互作用以导致认知障碍,可能会带来关于发病机制的新思维方式,并可能为早期认知障碍、痴呆和AD的治疗与预防提供新方法,而目前我们对这些疾病仍没有有效的治疗方法。