Alzheimer's disease: from basic science to precision medicine approach.
Alzheimer's disease: from basic science to precision medicine approach.
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DOI：
10.1136/bmjno-2020-000079
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发表时间：
2020
影响因子：
2.7
通讯作者：
Forloni G
中科院分区：
文献类型：
--
作者：
Forloni G
阿尔茨海默病（AD）是老年人最常见的痴呆症。除了脑淀粉样蛋白积累之外，还有多种因素导致 AD 病理，包括血管改变、全身炎症、遗传/表观遗传状态和线粒体功能障碍。目前，人们正在大力研究神经炎症。然而，抗炎药物和许多其他疗法一样，主要针对β-淀粉样蛋白，未能在AD中显示出有效的效果。时机、正确选择患者以及对多靶点方法的需求似乎是当前治疗工作的主要弱点。如果有有效的生物标志物，可以更好地评估治疗的效果。我们在此建议在 AD 中应用精准医学原理，根据个性化定制的生物标志物引导的靶向治疗，同时验证治疗的疗效和特定生物标志物的可靠性。有患AD风险或处于疾病早期阶段的人应根据以下方面进行分层：（1）神经心理学测试； (2) 载脂蛋白E(ApoE)基因分型； (3)血浆和脑脊液(CSF)的生化分析； (4) MRI 和正电子发射断层扫描，(5) 通过整合血浆、脑脊液中的各种遗传和生化参数以及微生物群组成分析来评估其炎症特征。选定的人群应在随机、纵向、安慰剂对照研究中使用特殊概况（例如血管概况、线粒体概况等）接受抗淀粉样蛋白生成和抗炎药物治疗。如果这些标准被广泛采用并共享结果，则有可能快速开发创新和个性化的药物治疗方案，并具有更现实的有效机会。
Alzheimer’s disease (AD) is the most common form of dementia in the elderly. Together with cerebral amyloid accumulation, several factors contribute to AD pathology including vascular alterations, systemic inflammation, genetic/epigenetic status and mitochondrial dysfunction. Much is now being devoted to neuroinflammation. However, anti-inflammatory drugs as numerous other therapies, mainly targeted on β-amyloid, have failed to show efficacious effects in AD. Timing, proper selection of patients, and the need for a multitarget approach appear to be the main weak points of current therapeutic efforts. The efficacy of a treatment could be better evaluate if efficient biomarkers are available. We propose here the application of precision medicine principles in AD to simultaneously verify the efficacy of a treatment and the reliability of specific biomarkers according to individually tailored biomarker-guided targeted therapies. People at risk of developing AD or in the very early phase of the disease should be stratified according to: (1) neuropsychological tests; (2) apolipoprotein E (ApoE) genotyping; (3) biochemical analysis of plasma and cerebrospinal fluid (CSF); (4) MRI and positron emission tomography and (5) assessment of their inflammatory profile by an integration of various genetic and biochemical parameters in plasma, CSF and an analysis of microbiota composition. The selected population should be treated with antiamyloidogenic and anti-inflammatory drugs in randomised, longitudinal, placebo-controlled studies using ad hoc profiles (eg, vascular profile, mitochondrial profile, etc…) If these criteria are adopted widely and the results shared, it may be possible to rapidly develop innovative and personalised drug treatment protocols with more realistic chances of being efficacious.
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影响因子：
12.7
作者：
Braak, Heiko;Del Tredici, Kelly
通讯作者：
Del Tredici, Kelly
DOI：
10.3233/jad-170819
发表时间：
2018
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Forloni G;Balducci C
通讯作者：
Balducci C
DOI：
10.1084/jem.20200861
发表时间：
2020-11-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Barthélemy NR;Horie K;Sato C;Bateman RJ
通讯作者：
Bateman RJ
HFE基因变体，铁和脂质：阿尔茨海默氏病的新型联系。
影响因子：
5.6
作者：
Ali-Rahmani F;Schengrund CL;Connor JR
通讯作者：
Connor JR
DOI：
10.1016/s1474-4422(17)30299-5
发表时间：
2017-11
期刊：
The Lancet. Neurology
影响因子：
--
作者：
GBD 2015 Neurological Disorders Collaborator Group
通讯作者：
GBD 2015 Neurological Disorders Collaborator Group