Department of Radiology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Department of Neurology, Hope Center for Neurological Disorders, and Knight Alzheimer's Disease Research Center, Washington University, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
Neuron. 2013 Dec 18;80(6):1347-58. doi: 10.1016/j.neuron.2013.12.003.
Alzheimer's disease (AD) is a slowly progressing disorder in which pathophysiological abnormalities, detectable in vivo by biomarkers, precede overt clinical symptoms by many years to decades. Five AD biomarkers are sufficiently validated to have been incorporated into clinical diagnostic criteria and commonly used in therapeutic trials. Current AD biomarkers fall into two categories: biomarkers of amyloid-β plaques and of tau-related neurodegeneration. Three of the five are imaging measures and two are cerebrospinal fluid analytes. AD biomarkers do not evolve in an identical manner but rather in a sequential but temporally overlapping manner. Models of the temporal evolution of AD biomarkers can take the form of plots of biomarker severity (degree of abnormality) versus time. In this Review, we discuss several time-dependent models of AD that take into consideration varying age of onset (early versus late) and the influence of aging and co-occurring brain pathologies that commonly arise in the elderly.
阿尔茨海默病（AD）是一种进展缓慢的疾病，其病理生理异常可通过生物标志物在体内检测到，这些异常在明显的临床症状出现之前可提前数年甚至数十年出现。目前有 5 种 AD 生物标志物已得到充分验证，被纳入临床诊断标准，并广泛用于治疗试验。目前的 AD 生物标志物分为两类：淀粉样蛋白-β斑块生物标志物和与 tau 相关的神经退行性变生物标志物。其中 5 种中的 3 种是影像学检测指标，2 种是脑脊液分析物。AD 生物标志物的演变并不完全相同，而是以顺序但时间上重叠的方式进行。AD 生物标志物的时间演变模型可以采用生物标志物严重程度（异常程度）与时间的关系图的形式。在这篇综述中，我们讨论了几种考虑到发病年龄（早发性与晚发性）以及与衰老和常见于老年人的并存脑部病变的影响的 AD 时间依赖性模型。
