Alzheimer's & Dementia:如何做到在2025年预防阿尔茨海默病:目标-风险-AD-预防(TRAP)战略简析

2021-09-20 haibei MedSci原创

在这些候选治疗药物中,有16种有一个以上的临床研究支持该药物能够降低AD风险。在降脂、抗炎、激素和代谢相关的药物类别中,出现了具有高置信度的排名靠前的治疗药物。

阿尔茨海默病(AD)是一种进行性的神经退行性疾病,可以导致认知和神经障碍,最终导致患者丧失自主性和独立生活能力。据估计,65岁以上的人中有11%会发展成AD。 目前,仅在美国估计就有高达620万的AD患者,预计到2050年这个数字将增加到1380万,而那时全世界将有1.52亿AD患者。值得注意的是,女性一生中患AD的风险是男性的2倍,占该疾病患者的60%以上

2011年,作为国家阿尔茨海默病项目法案(NAPA)的一部分,国家应对阿尔茨海默病计划被签署成为法律,目标是在2025年前预防和有效治疗阿尔茨海默病。由于导致阿尔茨海默病的潜在机制可能在诊断前20年就已经发生,因此预防和延缓该疾病的机会之窗非常大。虽然双盲安慰剂对照的AD预防试验在2025年之前无法执行,但根据临床护理标准,有可能确定针对AD风险因素的治疗方法对AD风险的影响。据预测,如果2020年,AD发病时间推迟1年,将导致2050年大约减少900万病例

最近,研究人员采用文本挖掘和自然语言处理策略的新组合,在PubMed数据库中识别(1)AD风险因素,(2)可针对风险因素途径的治疗方法,以及(3)支持治疗方法的研究。为了对与AD预防策略相关的文献进行分类,研究人员开发了基于STRING(检索相互作用基因/蛋白质的搜索工具)的蛋白质-蛋白质相互作用的相关性评分(RS)和基于贝叶斯推理的可信度评分(CS)。此外,为了解决作用机制问题,研究人员还对有效药物的蛋白质靶点进行了网络分析。总的来说,这种分析方法被称为目标-风险-AD-预防(TRAP)策略,其可以给出减少AD风险的候选疗法的排名列表。

得到临床研究支持的降低阿尔茨海默病(AD)风险的药物

研究人员根据TRAP对9625篇出版物的挖掘,确定了364个AD风险因素。根据风险因素的适应症,确定了629种食品和药物管理局批准的药物。而后,研究人员通过计算排名分数,确定了46种与降低AD风险有关的高可信度(RS和CS>0.7)药物。在这些候选治疗药物中,有16种有一个以上的临床研究支持该药物能够降低AD风险在降脂、抗炎、激素和代谢相关的药物类别中,出现了具有高置信度的排名靠前的治疗药物

因此,这个新的生物信息学策略的结果支持针对AD相关风险因素的生物机制和路径的治疗,并具有较高的可信度。针对与AD风险增加相关的途径的早期干预措施有可能帮助实现2025年有效预防AD的目标。

 

原始出处:

Francesca Vitali et al. Preventing Alzheimer's disease within reach by 2025: Targeted-risk-AD-prevention (TRAP) strategy. Alzheimer's & Dementia (2021). 

 

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    2022-05-15 bsmagic9140
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    2022-04-07 xue8602
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    2021-09-22 我思故我在2

    收获很大

    0

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Alzheimer's & Dementia:心血管风险负担与痴呆症和脑部病变风险的关系:基于人口的队列研究 

该研究表明,较高的FGCRS与痴呆和AD痴呆的风险增加有关。大脑中的血管和AD病变都可能是这种关联的基础。

Alzheimer's & Dementia:EXERT试验招募经验:有氧运动如何影响患有失忆性轻度认知障碍的老年人?

最近,研究人员描述了在招募患有MCI的成年人参加EXERT试验中所遇到的成功和挑战。

Alzheimer's & Dementia:多基因评分预测表型极端的APOE ε4携带者患阿尔茨海默病的风险 

研究人员评估了年龄≥75岁的认知健康的APOE ε4同型者(n = 213)和年龄≤65岁的早发APOE ε4同型AD病例(n = 223)之间的多基因风险评分(PRS)。

拓展阅读

Translational Neurodegeneration:复方代谢激活剂可用于治疗AD

阿尔茨海默病(AD)与神经退行性变关键因素相关的代谢异常有关。阿尔茨海默病的特征是进行性突触和轴突功能障碍、神经元丢失和认知能力下降。越来越多的证据表明,AD与代谢异常和氧化应激密切相关,氧化应激与神

Annals of neurology:人类血液代谢组与阿尔茨海默病风险之间的关系

谷氨酰胺可能是预防和治疗AD的一个有希望的目标

Alzheimer's & Dementia:结合血浆生物标志物的临床预测模型性能最佳

结合血浆生物标志物(尤其是p-tau217)的临床预测模型表现出较高的性能,且不受随机误差的影响。

睡眠是否影响认知功能

通过可穿戴设备记录家庭睡眠,提供睡眠表型的深度表征,可能有助于在正确的时间针对正确的患者进行靶向治疗。

Aging Cell:维生素D受体激活可能会增加阿尔茨海默病风险

VDR水平的异常增加被发现与Aβ斑块、胶质增生和自噬体共同定位,暗示VDR在AD发病机制中的非基因组激活。

Nat Aging:APOE等位基因在老年痴呆患者中左右神经炎症状态

研究人员通过研究APOE等位基因对没有神经淀粉样斑块的老年对照大脑的胶质转录组的影响,测试了APOE等位基因对胶质反应有不同影响的假设。