Increased CSF cortisol in AD is a function of APOE genotype
Increased CSF cortisol in AD is a function of APOE genotype
复制标题
DOI：
10.1212/wnl.56.8.1094
复制
发表时间：
2001-04-24
期刊：
影响因子：
9.9
通讯作者：
Raskind, MA
中科院分区：
文献类型：
--
作者：
Peskind, ER;Wilkinson, CW;Raskind, MA
背景资料：在AD中观察到下丘脑-垂体-肾上腺（HPA）轴活动增加，表现为皮质醇水平升高，并可能通过降低神经元变性的阈值而导致AD。APOE-ε 4等位基因的存在会增加AD的风险。在apoE基因缺陷小鼠中皮质醇浓度的增加表明，APOE基因型可能会影响AD患者的皮质醇浓度。研究方法：作者测定了64例AD患者和34例非痴呆老年对照者的CSF皮质醇水平和APOE基因型。结果：AD患者CSF皮质醇水平显著高于对照组。在4D受试者（ε 3/ε 4> ε 3/ε 4> ε 3/ε 3）和正常老年对照受试者（ε 3/ε 4> ε 3/ε 3> ε 3/ε 3）中，APOE基因型导致CSF皮质醇浓度不同。在ε 3/ε 4和ε 3/ε 3基因型内CSF皮质醇浓度的比较显示AD和对照受试者组之间没有差异。结论：与对照组相比，AD患者CSF皮质醇浓度升高与APOE-ε 4等位基因频率增加和APOE-ε 2等位基因频率降低相关。APOE基因型对HPA轴活性的影响可能与携带APOE-ε 4等位基因的人4D风险增加和携带APOE-ε 2等位基因的人AD风险降低有关。
Background: Increased hypothalamic-pituitary-adrenal (HPA) axis activity manifested by elevated cortisol levels is observed in AD and may contribute to AD by lowering the threshold for neuronal degeneration. Presence of the APOE-epsilon4 allele increases risk for AD. Increased cortisol concentrations in apoE-deficient mice suggest that APOE genotype may influence cortisol concentrations in AD. Methods: The authors measured cortisol levels in CSF and determined APOE genotypes for 64 subjects with AD and 34 nondemented older control subjects, Results: CSF cortisol was significantly higher in AD than in control subjects. CSF cortisol concentrations differed with respect to APOE genotype in both subjects with,4D (epsilon/epsilon4 > epsilon3/4 epsilon > epsilon3/epsilon3) and normal older control subjects (epsilon3/epsilon4 > epsilon3/epsilon3 > epsilon3/epsilon3). Comparison of CSF cortisol concentrations within the epsilon3/epsilon4 and epsilon3/epsilon3 genotypes revealed no differences between AD and control subject groups. Conclusions: Higher CSF cortisol concentrations were associated with increased frequency of the APOE-epsilon4 allele and decreased frequency of the,APOE-epsilon2 allele in AD subjects relative to control subjects. This effect of APOE genotype on HPA axis activity may be related to the increased risk for 4D in persons carrying the APOE-epsilon4 allele and decreased risk for AD in persons carrying the APOE-epsilon2 allele.