阿尔茨海默病预防及治疗性疫苗的研究进展

Prophylactic and Therapeutic Vaccines Against Alzheimer's Disease

1999年 ,用人体内源性的 β 淀粉样蛋白 (Aβ)主动免疫 ,引发自身免疫来预防和治疗阿尔茨海默病淀粉样蛋白沉积症的新策略 ,在动物实验中获得了巨大成功 ,从而开辟了AD研究的全新领域 ,也对传统的免疫学自身耐受理论提出了挑战。虽然主动免疫在体内清除Aβ沉积的机制尚不清楚 ,这个方法仍然在 2 0 0 1年迅速走入了临床试验。主动免疫在绝大多数病人体内有效地诱发出具有高度选择特异性的抗 Aβ的抗体 ,并且可以观察到类似于动物实验所显示的清除脑部Aβ沉积的巨大作用 ,使人们看到了征服AD的希望。但伴之出现的部分中枢神经系统炎症病例却使此项临床试验被终止。AD主动免疫治疗的动物实验、人体实验及相关机理研究近年进展极快 ,是一个深具发展潜力的新领域。

amyloid(Aβ)immunization as vaccines has now become a promising approach for the prevention and treatment of Alzheimer's disease(AD)after its debut in 1999.Transgenic mouse models of AD that develop age-dependent Aβ deposition, damage to the neuropil, and behavioral deficits have enabled researchers to test if the approach can influence these AD-like pathologic changes in their brains. Active immunization with different forms of A β and protocols have been shown to decrease brain Aβ deposition and improve cognitive performance in these mice models in the following studies. Although the phaseⅡclinical trials of active immunization with Aβ(AN1792)were halted last year due to the occurrence of CNS inflammation in a small subset of patients, researchers found that strong humoral responses can be induced by the vaccination. Furthermore, the active immunization also brings an almost complete clearance of Aβ from much of the cerebral cortex. Aβ specific antibodies are believed to cross blood-brain barrier by minimal destroy of vascular wall where amyloid depositions exist. Three possible mechanisms on removal of Aβ deposition from brain have also been reviewed. Still some problems should be clarified before this strategy could be applied for clinical therapy. Whether vaccination will improve the cognitive decline in AD patients will depend upon clinical assessments, which was vital to destiny of the approach.