Biomarkers for Alzheimer's Disease (AD) and the Application of Precision Medicine.
Biomarkers for Alzheimer's Disease (AD) and the Application of Precision Medicine.
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阿尔茨海默病（AD）的生物标志物及其精准医学的应用。
DOI：
10.3390/jpm10030138
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发表时间：
2020-09-21
影响因子：
--
通讯作者：
Zhao Y
中科院分区：
文献类型：
--
作者：
Lukiw WJ;Vergallo A;Lista S;Hampel H;Zhao Y
阿尔茨海默病（AD）的准确诊断目前是所有临床神经病学中最困难和最具挑战性的问题之一。 AD 通常通过综合知识以及对多种生物标志物和相关因素的评估来诊断。这些包括患者的年龄、性别和生活方式、病史和遗传史（临床和家族史）、认知、身体、行为和老年评估、多种AD患者生物体液的实验室检查，特别是体循环（血清）和脑脊液（CSF）内的生物体液、大脑边缘系统和/或视网膜的多种神经影像学模式，在许多情况下通过死后神经病理学检查进行随访，以最终证实诊断。通常，前瞻性 AD 病例伴有其他进行性、与年龄相关的痴呆性神经病理学，主要包括神经血管和/或心血管成分、多发性梗塞性痴呆 (MID)、额颞叶痴呆 (FTD) 和/或中风或“小中风”，通常与其他与年龄相关的神经系统和非神经系统疾病（包括心血管疾病和癌症）相结合。特别是在过去的 40 年里，人们进行了大量的研究工作来发现、表征和量化更有效和可靠的 AD 生物标志物，特别是在 AD 的临床前或前驱阶段，以便可以启动先发制人的治疗策略。虽然单个 AD 患者可以获得的大量遗传、神经生物学、神经化学、神经病理学、神经影像学和其他诊断信息可能是巨大的：(i) 目前，从这些多方面和多维度的信息中整合和制定 AD 的明确诊断是一项挑战； (ii) 不幸的是，即使仔细匹配年龄、性别、家族遗传学和药物史，这些数据也不能与其他 AD 患者的病因病理学模式直接比较。四十年的 AD 研究一再表明 AD 的诊断特征反映了一种极其异质的神经系统疾病。这篇评论将阐明 AD 生物标志物的异质性，评论新兴的研究方法，并讨论为什么“精准医学”正在成为我们迄今为止对这种阴险且致命的脑部疾病进行最准确和明确的预测、诊断和预后的最佳范例。
An accurate diagnosis of Alzheimer’s disease (AD) currently stands as one of the most difficult and challenging in all of clinical neurology. AD is typically diagnosed using an integrated knowledge and assessment of multiple biomarkers and interrelated factors. These include the patient’s age, gender and lifestyle, medical and genetic history (both clinical- and family-derived), cognitive, physical, behavioral and geriatric assessment, laboratory examination of multiple AD patient biofluids, especially within the systemic circulation (blood serum) and cerebrospinal fluid (CSF), multiple neuroimaging-modalities of the brain’s limbic system and/or retina, followed up in many cases by post-mortem neuropathological examination to finally corroborate the diagnosis. More often than not, prospective AD cases are accompanied by other progressive, age-related dementing neuropathologies including, predominantly, a neurovascular and/or cardiovascular component, multiple-infarct dementia (MID), frontotemporal dementia (FTD) and/or strokes or ‘mini-strokes’ often integrated with other age-related neurological and non-neurological disorders including cardiovascular disease and cancer. Especially over the last 40 years, enormous research efforts have been undertaken to discover, characterize, and quantify more effectual and reliable biological markers for AD, especially during the pre-clinical or prodromal stages of AD so that pre-emptive therapeutic treatment strategies may be initiated. While a wealth of genetic, neurobiological, neurochemical, neuropathological, neuroimaging and other diagnostic information obtainable for a single AD patient can be immense: (i) it is currently challenging to integrate and formulate a definitive diagnosis for AD from this multifaceted and multidimensional information; and (ii) these data are unfortunately not directly comparable with the etiopathological patterns of other AD patients even when carefully matched for age, gender, familial genetics, and drug history. Four decades of AD research have repeatedly indicated that diagnostic profiles for AD are reflective of an extremely heterogeneous neurological disorder. This commentary will illuminate the heterogeneity of biomarkers for AD, comment on emerging investigative approaches and discuss why ‘precision medicine’ is emerging as our best paradigm yet for the most accurate and definitive prediction, diagnosis, and prognosis of this insidious and lethal brain disorder.
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DOI：
10.1038/s41582-018-0079-7
发表时间：
2018-11
期刊：
Nature reviews. Neurology
影响因子：
--
作者：
Hampel H;O'Bryant SE;Molinuevo JL;Zetterberg H;Masters CL;Lista S;Kiddle SJ;Batrla R;Blennow K
通讯作者：
Blennow K
影响因子：
4.2
作者：
Guerreiro RJ;Gustafson DR;Hardy J
通讯作者：
Hardy J
影响因子：
3.4
作者：
Hill JM;Bhattacharjee S;Pogue AI;Lukiw WJ
通讯作者：
Lukiw WJ
影响因子：
14.5
作者：
Dong, Aoyan;Toledo, Jon B.;Davatzikos, Christos
通讯作者：
Davatzikos, Christos
影响因子：
4.7
作者：
Ellegaard Nielsen, Jonas;Sofie Pedersen, Kamilla;Pedersen, Shona
通讯作者：
Pedersen, Shona