Takeda Shuko
Department of Clinical Gene Therapy, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan.
Neurosci Res. 2019 Apr;141:36-42. doi: 10.1016/j.neures.2018.08.005. Epub 2018 Aug 16.
The number of patients with Alzheimer's disease (AD) has been increasing exponentially side by side with aging societies worldwide. Symptoms of AD worsen over time due to progressive neurodegeneration, requiring institutional care at the later stage and resulting in a heavy burden on patients, caregivers, and the public-health system. AD neuropathology is characterized by cerebral accumulation and aggregation of amyloid-β (Aβ) and tau proteins. For decades, Aβ has been a leading target in the therapeutic development for AD, and many drug candidates have been tested in clinical trials; however, most medications have failed to slow the progression of the disease. Tau pathology currently is attracting more attention as an alternate target for developing disease-modifying therapy. Tau is known to spread in a hierarchical pattern in AD brain, likely by trans-synaptic tau transfer between neurons. Extracellular tau may mediate tau spreading and serve as biomarker for AD. AD pathogenesis is multifactorial, and many genetic- and non-genetic factors are known to contribute to Aβ- and tau-related pathology. Recent studies indicate an association between vascular risk factors and AD. Identifying modifiable risk factors for AD and understanding their contributory mechanisms could be key in tackling this devastating disease.
随着全球老龄化社会的发展，阿尔茨海默病（AD）患者数量呈指数级增长。由于进行性神经退行性变，AD症状会随着时间恶化，在疾病后期需要机构护理，给患者、护理人员和公共卫生系统带来沉重负担。AD神经病理学的特征是淀粉样β蛋白（Aβ）和tau蛋白在大脑中积累和聚集。几十年来，Aβ一直是AD治疗研发的主要靶点，许多候选药物已在临床试验中进行测试；然而，大多数药物未能减缓疾病进展。目前，tau病理学作为开发疾病修饰疗法的替代靶点正受到更多关注。已知tau在AD大脑中以分层模式传播，可能是通过神经元之间的跨突触tau转移。细胞外tau可能介导tau传播，并作为AD的生物标志物。AD发病机制是多因素的，许多遗传和非遗传因素已知会导致与Aβ和tau相关的病理学。最近的研究表明血管危险因素与AD之间存在关联。识别AD的可改变危险因素并了解其作用机制可能是攻克这种毁灭性疾病的关键。
