Nathan Kline Institute, Orangeburg, NY, USA.
Psychoneuroendocrinology. 2012 Mar;37(3):366-71. doi: 10.1016/j.psyneuen.2011.07.006. Epub 2011 Jul 30.
Abnormalities of the hypothalamic-pituitary-adrenal (HPA) axis have been reported in subjects with Alzheimer's disease (AD) and may include increased cerebrospinal fluid (CSF) cortisol concentrations. Moreover, presence of the APOE ɛ4 allele, which is an established risk factor for the development of AD, has been shown to associate with higher CSF cortisol levels, especially in AD sufferers. In this study, we examined whether TOMM40 variants, which have been reported to influence age of onset of AD, also had an effect on CSF cortisol levels, in healthy, cognitively intact individuals with or without APOE ɛ4. In our results, the increase in CSF cortisol associated with the presence of the APOE ɛ4 allele was only detected when a short TOMM40 poly-T variant, shown to associate with later age of onset of AD in ɛ4 carriers, was not present. These results are consistent with previous reports (e.g., Roses et al., 2009) suggesting that TOMM40 poly-T variants influence the effects of APOE alleles.
已有研究报道，阿尔茨海默病（AD）患者的下丘脑-垂体-肾上腺（HPA）轴存在异常，这可能包括脑脊液（CSF）中皮质醇浓度升高。此外，载脂蛋白 E4（APOE ɛ4）等位基因是 AD 发病的既定危险因素，已有研究表明，该等位基因与较高的 CSF 皮质醇水平相关，尤其是在 AD 患者中。在这项研究中，我们研究了载脂蛋白 E4（APOE ɛ4）携带者中，与 AD 发病年龄相关的 TOMM40 变异是否也会影响 CSF 皮质醇水平，这些携带者是健康的、认知功能完整的个体。我们的研究结果表明，当携带较短的 TOMM40 多态性 T 时，与 AD 发病年龄较晚相关，与 APOE ɛ4 等位基因相关的 CSF 皮质醇升高仅被检测到。这些结果与之前的研究结果一致（例如，Roses 等人，2009 年），表明 TOMM40 多态性 T 变体影响 APOE 等位基因的作用。
