Yanagida Kanta, Tagami Shinji, Okochi Masayasu
Department of Psychiatry, Graduate School of Medicine, Osaka University.
Brain Nerve. 2017 Jul;69(7):825-833. doi: 10.11477/mf.1416200826.
To cope with an aging society, development of disease-modifying drugs for Alzheimer's disease (AD) is essential. Currently, only symptomatic treatments that suppress clinical manifestations are available. Amyloid-β (Aβ) is an AD-related pathogenic molecule that triggers development of AD pathology; thus, decreasing Aβ in the brain is a promising candidate for AD therapy. Numerous pharmaceutical companies have developed therapeutic drugs against Aβ, such as β-secretase inhibitors, γ-secretase inhibitors, and anti-Aβ monoclonal antibodies, but in clinical trials for patients with mild to moderate AD, these drugs did not meet the expected endpoints. These results suggest that earlier administration of these drugs to individuals who have not yet developed cognitive decline, but have AD pathological changes in the brain or high risk of developing these changes, may be beneficial. To enable such early treatment, preclinical AD biomarkers are required. In this review, we comment on current AD biomarkers in cerebrospinal fluid and in blood. We also explain CSF/blood APL1β, which is a candidate surrogate marker for Aβ in the brain.
为应对社会老龄化,开发用于治疗阿尔茨海默病(AD)的疾病修饰药物至关重要。目前,仅有抑制临床表现的对症治疗方法。淀粉样β蛋白(Aβ)是一种与AD相关的致病分子,可引发AD病理发展;因此,降低大脑中的Aβ是AD治疗的一个有前景的候选方法。众多制药公司已开发出针对Aβ的治疗药物,如β-分泌酶抑制剂、γ-分泌酶抑制剂和抗Aβ单克隆抗体,但在针对轻至中度AD患者的临床试验中,这些药物未达到预期终点。这些结果表明,对于尚未出现认知衰退,但大脑已出现AD病理变化或有发生这些变化的高风险个体,更早使用这些药物可能有益。为实现这种早期治疗,需要临床前AD生物标志物。在本综述中,我们对目前脑脊液和血液中的AD生物标志物进行评论。我们还解释了脑脊液/血液中的APL1β,它是大脑中Aβ的候选替代标志物。