Rafii Michael S, Ances Beau M, Schupf Nicole, Krinsky-McHale Sharon J, Mapstone Mark, Silverman Wayne, Lott Ira, Klunk William, Head Elizabeth, Christian Brad, Lai Florence, Rosas H Diana, Zaman Shahid, Petersen Melissa E, Strydom Andre, Fortea Juan, Handen Benjamin, O'Bryant Sid
Alzheimer's Therapeutic Research Institute (ATRI) Keck School of Medicine University of Southern California San Diego California USA.
Center for Advanced Medicine Neuroscience Washington University School of Medicine in St. Louis St. Louis Missouri USA.
Alzheimers Dement (Amst). 2020 Oct 27;12(1):e12062. doi: 10.1002/dad2.12062. eCollection 2020.
The National Institute on Aging in conjunction with the Alzheimer's Association (NIA-AA) recently proposed a biological framework for defining the Alzheimer's disease (AD) continuum. This new framework is based upon the key AD biomarkers (amyloid, tau, neurodegeneration, AT[N]) instead of clinical symptoms and represents the latest understanding that the pathological processes underlying AD begin decades before the manifestation of symptoms. By using these same biomarkers, individuals with Down syndrome (DS), who are genetically predisposed to developing AD, can also be placed more precisely along the AD continuum. The A/T(N) framework is therefore thought to provide an objective manner by which to select and enrich samples for clinical trials. This new framework is highly flexible and allows the addition of newly confirmed AD biomarkers into the existing AT(N) groups. As biomarkers for other pathological processes are validated, they can also be added to the AT(N) classification scheme, which will allow for better characterization and staging of AD in DS. These biological classifications can then be merged with clinical staging for an examination of factors that impact the biological and clinical progression of the disease. Here, we leverage previously published guidelines for the AT(N) framework to generate such a plan for AD among adults with DS.
美国国立衰老研究所与阿尔茨海默病协会(NIA-AA)最近提出了一个用于定义阿尔茨海默病(AD)连续体的生物学框架。这个新框架基于关键的AD生物标志物(淀粉样蛋白、tau蛋白、神经退行性变、AT[N])而非临床症状,代表了一种最新认识,即AD潜在的病理过程在症状出现前数十年就已开始。通过使用这些相同的生物标志物,患有唐氏综合征(DS)且有患AD遗传倾向的个体也能更精确地置于AD连续体中。因此,A/T(N)框架被认为提供了一种客观方式来为临床试验选择和富集样本。这个新框架具有高度灵活性,允许将新确认的AD生物标志物添加到现有的AT(N)组中。随着用于其他病理过程的生物标志物得到验证,它们也可以添加到AT(N)分类方案中,这将有助于更好地对DS中的AD进行特征描述和分期。然后,这些生物学分类可以与临床分期相结合,以研究影响该疾病生物学和临床进展的因素。在此,我们利用先前发布的关于AT(N)框架的指南,为患有DS的成年人制定这样一个针对AD的计划。