Biomarker-based diagnosis of preclinical Alzheimer disease: time for the clinic?
Biomarker-based diagnosis of preclinical Alzheimer disease: time for the clinic?
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DOI：
10.1038/s41582-022-00767-x
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发表时间：
2023-02
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据估计，全球有 55-6000 万人患有痴呆症，预计到 20501 年这一数字将增加两倍。这些数字强调迫切需要找到有效的痴呆症治疗方法；然而，在普通人群中有效部署痴呆症疗法的一个主要障碍是缺乏使用客观的疾病相关生物标志物的临床验证的诊断方法。阿尔茨海默病 (AD) 是最常见的痴呆类型，占所有病例的 60-80%。在 AD 大脑中观察到的两种典型病理学是淀粉样蛋白-β 肽的细胞外沉积物（形成典型老年斑的骨干）和异常、过度磷酸化 tau 蛋白的神经元内积聚，这些蛋白聚集成神经原纤维缠结 2。目前的 AD 发病机制模型描述了大脑病理的出现早于临床可测量的认知症状3，这表明在认知未受损的临床前 AD 个体中检测 AD 相关生物标志物应该是可能的。在过去 20 年中，技术创新已经允许使用 PET 检测活体个体大脑中的淀粉样蛋白和 tau 蛋白聚集物。此外，2016 年发布了一个框架，根据淀粉样蛋白 (A)、tau (T) 和神经变性 (N) 生物标志物的组合对个体进行分层——每个生物标志物的个体可以是阳性或阴性4。这个最初以研究为导向的“ATN”框架旨在改善临床试验中的招募，并源自美国国家老龄化研究所、阿尔茨海默病协会和 AD 国际工作组制定的 AD 临床定义的最新标准。此后，ATN 框架已被证明在研究环境中有效7，下一个问题是它是否可以应用于医疗实践，以诊断整个 AD 连续体中的个体，并评估从临床前 AD 进展为痴呆的风险。事实上，处于临床前阶段的个体最有可能从未来的预防性治疗中受益。在一项新研究中，Rik Ossenkoppele 及其同事5询问淀粉样蛋白和 tau PET 的预测效果如何
An estimated 55–60 million individuals have dementia globally and this number is expected to triple by 20501. These figures emphasize the urgent need to identify effective dementia treatments; however, a major hindrance to the efficient deployment of dementia therapies in the general population is the lack of clinically validated diagnostic methods that use objective, disease-associated biomarkers. Alzheimer disease (AD) is the most common type of dementia and accounts for 60–80% of all cases. The two canonical pathologies observed in the AD brain are extracellular deposits of amyloid-β peptides, which form the backbone of prototypical senile plaques, and the intraneuronal accumulation of abnormal, hyperphosphorylated tau proteins, which aggregate into neurofibrillary tangles2. The current model of AD pathogenesis describes the appearance of brain pathologies several years before clinically measurable cognitive symptoms3, suggesting that the detection of AD-associated biomarkers should be possible in cognitively unimpaired individuals with preclinical AD.In the past 2 decades, technological innovations have permitted the detection of amyloid and tau aggregates in the brain of living individuals using PET. Furthermore, in 2016, a framework was published that stratified individuals on the basis of a combination of amyloid (A), tau (T), and neurodegeneration (N) biomarkers—an individual can be either positive or negative for each biomarker4. This originally research-oriented ‘ATN’framework was designed to improve recruitment in clinical trials and was derived from the most recent criteria for the clinical definition of AD by the National Institute on Aging, the Alzheimer’s Association and the AD International Working Group. The ATN framework has since proven efficient in research settings7 and the next question is whether it can be applied to medical practice to diagnose individuals across the entire continuum of AD, and to assess risk of progression from preclinical AD to dementia. Indeed, individuals at the preclinical stage are the most likely to benefit from future preventative therapies. In a new study, Rik Ossenkoppele and colleagues5 asked how well amyloid and tau PET could predict
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作者：
Wilkins, Consuelo H.;Windon, Charles C.;Dilworth-Anderson, Peggye;Romanoff, Justin;Gatsonis, Constantine;Hanna, Lucy;Apgar, Charles;Gareen, Ilana F.;Hill, Carl, V;Hillner, Bruce E.;March, Andrew;Siegel, Barry A.;Whitmer, Rachel A.;Carrillo, Maria C.;Rabinovici, Gil D.
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Rabinovici, Gil D.
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14
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影响因子：
29
作者：
Strikwerda-Brown, Cherie;Hobbs, Diana A.;Villeneuve, Sylvia
通讯作者：
Villeneuve, Sylvia
影响因子：
9.9
作者：
van der Kall LM;Truong T;Burnham SC;Doré V;Mulligan RS;Bozinovski S;Lamb F;Bourgeat P;Fripp J;Schultz S;Lim YY;Laws SM;Ames D;Fowler C;Rainey-Smith SR;Martins RN;Salvado O;Robertson J;Maruff P;Masters CL;Villemagne VL;Rowe CC
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Rowe CC