Duke University, Durham, NC, USA; Zinfandel Pharmaceuticals, Durham, NC, USA.
Alzheimers Dement. 2013 Mar;9(2):132-6. doi: 10.1016/j.jalz.2012.10.009. Epub 2013 Jan 18.
A number of recent studies have not replicated the association of the translocase of the outer mitochondrial membrane pore subunit (TOMM40) rs10524523 polymorphism, which is in linkage disequilibrium with apolipoprotein E (APOE), with age of onset of Alzheimer's disease (AD). This perspective describes the differences between these later studies and the original experiments. We highlight the necessity for using standardized and informative assessment tools and processes when determining the age of development of AD or AD symptoms, and also stress that this clinical phenotype is best measured reliably in prospective studies during which subjects are monitored over time. This is true when assessing potential biomarkers for age of onset and when assessing the therapeutic potential of medicines that may delay the onset or progression of this disease.
一些最近的研究未能复制外膜孔转运蛋白（TOMM40）rs10524523 多态性与载脂蛋白 E（APOE）之间的关联，该多态性与载脂蛋白 E（APOE）呈连锁不平衡，与阿尔茨海默病（AD）的发病年龄有关。本观点描述了这些后续研究与原始实验之间的差异。我们强调在确定 AD 或 AD 症状的发病年龄时，使用标准化和信息丰富的评估工具和程序的必要性，同时也强调这种临床表型最好在对受试者进行长期监测的前瞻性研究中可靠地测量。当评估发病年龄的潜在生物标志物和评估可能延缓这种疾病发病或进展的药物的治疗潜力时，这是正确的。
