Department of Neurology, Hope Center for Neurological Disorders, and Knight Alzheimer's Disease Research Center, Washington University, St. Louis, Missouri 63110.
Cold Spring Harb Perspect Med. 2017 Oct 3;7(10):a024331. doi: 10.1101/cshperspect.a024331.
The astonishing findings that active and passive immunization against amyloid-β (Aβ) in mouse models of Alzheimer's disease (AD) dramatically decreased amyloid burden led to a rapid initiation of human clinical trials with much enthusiasm. However, methodological issues and adverse effects relating to these clinical trials arose, challenging the effectiveness and safety of these reagents. Efforts are now underway to develop safer immunotherapeutic approaches toward Aβ and the treatment of individuals at risk for AD before or in the earliest stages of cognitive decline with new hopes. Furthermore, several studies have shown tau as a potential immunotherapeutic target for the treatment of tauopathy-related diseases including frontotemporal lobar dementia (FTLD). Both active and passive immunization targeting tau in mouse models of tauopathy effectively decreased tau pathology while improving cognitive performance. These preclinical studies have highlighted tau as an alternative target with much anticipation of clinical trials to be undertaken.
令人惊讶的发现,在阿尔茨海默病(AD)的小鼠模型中,针对淀粉样蛋白-β(Aβ)的主动和被动免疫显著降低了淀粉样蛋白负担,这使得人们非常兴奋地迅速启动了人类临床试验。然而,这些临床试验出现了与方法学问题和不良反应相关的问题,这对这些试剂的有效性和安全性提出了挑战。目前正在努力开发更安全的针对 Aβ的免疫治疗方法,并在认知能力下降的早期或之前,为有患 AD 风险的个体提供新的希望。此外,几项研究表明,tau 是治疗包括额颞叶痴呆(FTLD)在内的与 tau 病相关疾病的潜在免疫治疗靶点。在 tau 病的小鼠模型中针对 tau 的主动和被动免疫都能有效降低 tau 病理学,同时改善认知表现。这些临床前研究强调了 tau 作为替代靶点的重要性,人们期待着开展临床试验。