Biomarkers: Our Path Towards a Cure for Alzheimer Disease.
Biomarkers: Our Path Towards a Cure for Alzheimer Disease.
复制标题
DOI：
10.1177/1177271920976367
复制
发表时间：
2020
影响因子：
3.8
通讯作者：
Tarawneh R
中科院分区：
文献类型：
--
作者：
Tarawneh R
在过去的十年中，生物标志物显着提高了我们对阿尔茨海默病（AD）病理生理学的理解，并提供了有价值的工具来检查不同的疾病机制及其随时间的进展。虽然已经鉴定了AD中淀粉样蛋白、tau蛋白、神经元、突触和轴突损伤、炎症和免疫失调的几种标志物，但反映其他疾病机制（如氧化应激、线粒体损伤、血管或内皮损伤和钙介导的兴奋性毒性）的生物标志物相对缺乏。重要的是，迫切需要标准化不同中心的生物标志物评估方法，并确定动态生物标志物，这些生物标志物可以监测疾病随时间的进展和/或对潜在疾病改善治疗的反应。由国家老龄化研究所-阿尔茨海默氏症协会（NIA-AA）工作组提出的AD的最新研究框架强调了在AD研究中纳入生物标志物的重要性，并将AD定义为由淀粉样蛋白、tau蛋白和神经变性组成的生物结构，其跨越症状前和症状阶段。由于AD治疗药物的临床试验结果令人失望，因此越来越清楚的是，未来AD试验的成功将需要在参与者选择、筛选、监测疾病进展和评估治疗反应中纳入生物标志物。我们在这里回顾了流体AD生物标志物的现状，并讨论了最新的NIA-AA研究框架的优点和局限性。重要的是，通过系统生物学方法将生物标志物数据与临床、认知和成像领域整合，对于充分捕获AD的分子、遗传和病理异质性及其随时间的时空演变至关重要。
Over the last decade, biomarkers have significantly improved our understanding of the pathophysiology of Alzheimer disease (AD) and provided valuable tools to examine different disease mechanisms and their progression over time. While several markers of amyloid, tau, neuronal, synaptic, and axonal injury, inflammation, and immune dysregulation in AD have been identified, there is a relative paucity of biomarkers which reflect other disease mechanisms such as oxidative stress, mitochondrial injury, vascular or endothelial injury, and calcium-mediated excitotoxicity. Importantly, there is an urgent need to standardize methods for biomarker assessments across different centers, and to identify dynamic biomarkers which can monitor disease progression over time and/or response to potential disease-modifying treatments. The updated research framework for AD, proposed by the National Institute of Aging- Alzheimer’s Association (NIA-AA) Work Group, emphasizes the importance of incorporating biomarkers in AD research and defines AD as a biological construct consisting of amyloid, tau, and neurodegeneration which spans pre-symptomatic and symptomatic stages. As results of clinical trials of AD therapeutics have been disappointing, it has become increasingly clear that the success of future AD trials will require the incorporation of biomarkers in participant selection, prognostication, monitoring disease progression, and assessing response to treatments. We here review the current state of fluid AD biomarkers, and discuss the advantages and limitations of the updated NIA-AA research framework. Importantly, the integration of biomarker data with clinical, cognitive, and imaging domains through a systems biology approach will be essential to adequately capture the molecular, genetic, and pathological heterogeneity of AD and its spatiotemporal evolution over time.
登录
查看更多内容
影响因子：
15.1
作者：
Brinkmalm A;Brinkmalm G;Honer WG;Frölich L;Hausner L;Minthon L;Hansson O;Wallin A;Zetterberg H;Blennow K;Öhrfelt A
通讯作者：
Öhrfelt A
影响因子：
--
作者：
Begcevic I;Tsolaki M;Brinc D;Brown M;Martinez-Morillo E;Lazarou I;Kozori M;Tagaraki F;Nenopoulou S;Gkioka M;Lazarou E;Lim B;Batruch I;Diamandis EP
通讯作者：
Diamandis EP
影响因子：
11.4
作者：
Cheignon C;Tomas M;Bonnefont-Rousselot D;Faller P;Hureau C;Collin F
通讯作者：
Collin F
影响因子：
5.3
作者：
Abad, Maria A.;Enguita, Marta;Trullas, Ramon
通讯作者：
Trullas, Ramon
DOI：
10.1016/j.jalz.2013.10.005
发表时间：
2015-03
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
Chêne G;Beiser A;Au R;Preis SR;Wolf PA;Dufouil C;Seshadri S
通讯作者：
Seshadri S