Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
Int J Mol Sci. 2017 Sep 13;18(9):1965. doi: 10.3390/ijms18091965.
Brain capillary endothelial cells form the blood-brain barrier (BBB), which is covered with basement membranes and is also surrounded by pericytes and astrocyte end-feet in the neurovascular unit. The BBB tightly regulates the molecular exchange between the blood flow and brain parenchyma, thereby regulating the homeostasis of the central nervous system (CNS). Thus, dysfunction of the BBB is likely involved in the pathogenesis of several neurological diseases, including Alzheimer's disease (AD). While amyloid-β (Aβ) deposition and neurofibrillary tangle formation in the brain are central pathological hallmarks in AD, cerebrovascular lesions and BBB alteration have also been shown to frequently coexist. Although further clinical studies should clarify whether BBB disruption is a specific feature of AD pathogenesis, increasing evidence indicates that each component of the neurovascular unit is significantly affected in the presence of AD-related pathologies in animal models and human patients. Conversely, since some portions of Aβ are eliminated along the neurovascular unit and across the BBB, disturbing the pathways may result in exacerbated Aβ accumulation in the brain. Thus, current evidence suggests that BBB dysfunction may causatively and consequently contribute to AD pathogenesis, forming a vicious cycle between brain Aβ accumulation and neurovascular unit impairments during disease progression.
脑毛细血管内皮细胞形成血脑屏障（BBB），其被基底膜覆盖，同时也被神经血管单元中的周细胞和星形胶质细胞终足环绕。BBB 严格调控血流与脑组织间的分子交换，从而调节中枢神经系统（CNS）的内稳态。因此，BBB 功能障碍可能与包括阿尔茨海默病（AD）在内的多种神经退行性疾病的发病机制有关。虽然脑内淀粉样蛋白-β（Aβ）沉积和神经纤维缠结是 AD 的核心病理标志，但脑血管病变和 BBB 改变也已被证明常同时存在。尽管进一步的临床研究尚需阐明 BBB 破坏是否是 AD 发病机制的一个特定特征，但越来越多的证据表明，在动物模型和人类患者的 AD 相关病变中，神经血管单元的每个组成部分都受到显著影响。相反，由于 Aβ 的某些部分沿着神经血管单元和 BBB 被清除，干扰这些途径可能导致 Aβ 在脑中的积累加剧。因此，目前的证据表明，BBB 功能障碍可能是 AD 发病机制的原因和结果，在疾病进展过程中形成了脑内 Aβ 积累与神经血管单元损伤之间的恶性循环。
