Dementia Research Group, John James Laboratories, Frenchay Hospital, Institute of Clinical Neurosciences, School of Clinical Sciences, University of Bristol, Bristol, UK.
J Alzheimers Dis. 2012;30 Suppl 2:S269-82. doi: 10.3233/JAD-2012-111664.
Midlife hypertension is a risk factor for late onset Alzheimer's disease (AD) and it is one of the components of metabolic syndrome (MetS). Observational studies and some cardiovascular disease-related clinical trials suggest that antihypertensive treatment reduced the incidence and progression of AD. Calcium channel blockers (CCBs), one of the more commonly used treatments for hypertension, target voltage-gated calcium channels (VGCCs) which are found on neurons in the brain where calcium regulation is very important in both learning and memory. Amyloid-β (Aβ) peptide, one of the main pathological hallmarks of AD, causes increases to intracellular calcium via VGCCs, which in turn leads to further increases in Aβ production. Memantine, a current treatment used in AD, exerts some of its beneficial effects by blocking calcium entry into neurons. We explore the possibility of whether CCBs acting in the brain may delay the onset and progression of AD and thus may inform treatment regimes in people with MetS.
中年高血压是晚年发病的阿尔茨海默病(AD)的一个危险因素,也是代谢综合征(MetS)的组成部分之一。观察性研究和一些心血管疾病相关的临床试验表明,降压治疗可降低 AD 的发病率和进展。钙通道阻滞剂(CCB)是治疗高血压的常用药物之一,其作用靶点是位于大脑神经元上的电压门控钙通道(VGCC),钙调节在学习和记忆中非常重要。淀粉样β(Aβ)肽是 AD 的主要病理标志之一,它通过 VGCC 导致细胞内钙增加,进而导致 Aβ生成进一步增加。美金刚是一种用于 AD 的现有治疗药物,其部分有益作用是通过阻止钙进入神经元来实现的。我们探讨了 CCB 在大脑中发挥作用是否可能延迟 AD 的发病和进展,从而为 MetS 患者的治疗方案提供信息。