认知正常老年人中,睡眠呼吸障碍与载脂蛋白E基因型对阿尔茨海默病脑脊液生物标志物的相互作用。

Interaction between sleep-disordered breathing and apolipoprotein E genotype on cerebrospinal fluid biomarkers for Alzheimer's disease in cognitively normal elderly individuals.

作者信息

Osorio Ricardo S, Ayappa Indu, Mantua Janna, Gumb Tyler, Varga Andrew, Mooney Anne M, Burschtin Omar E, Taxin Zachary, During Emmanuel, Spector Nicole, Biagioni Milton, Pirraglia Elizabeth, Lau Hiuyan, Zetterberg Henrik, Blennow Kaj, Lu Shou-En, Mosconi Lisa, Glodzik Lidia, Rapoport David M, de Leon Mony J

机构信息

Center for Brain Health, NYU School of Medicine, New York, NY, USA; Alzheimer Disease Research Unit, CIEN Foundation, Carlos III Institute of Health, Alzheimer Center Reina Sofia Foundation, Madrid, Spain.

Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, NYU School of Medicine, New York, NY, USA.

出版信息

Neurobiol Aging. 2014 Jun;35(6):1318-24. doi: 10.1016/j.neurobiolaging.2013.12.030. Epub 2013 Dec 27.

Abstract

Previous studies have suggested a link between sleep disordered breathing (SDB) and dementia risk. In the present study, we analyzed the relationship between SDB severity, cerebrospinal fluid (CSF) Alzheimer's disease-biomarkers, and the ApoE alleles. A total of 95 cognitively normal elderly participants were analyzed for SDB severity, CSF measures of phosphorylated-tau (p-tau), total-tau (t-tau), and amyloid beta 42 (Aβ-42), as well as ApoE allele status. In ApoE3+ subjects, significant differences were found between sleep groups for p-tau (F[df2] = 4.3, p = 0.017), and t-tau (F[df2] = 3.3, p = 0.043). Additionally, among ApoE3+ subjects, the apnea and/or hypopnea with 4% O2-desaturation index was positively correlated with p-tau (r = 0.30, p = 0.023), t-tau (r = 0.31, p = 0.021), and Aβ-42 (r = 0.31, p = 0.021). In ApoE2+ subjects, the apnea and/or hypopnea with 4% O2-desaturation index was correlated with lower levels of CSF Aβ-42 (r = -0.71, p = 0.004), similarly to ApoE4+ subjects where there was also a trend toward lower CSF Aβ-42 levels. Our observations suggest that there is an association between SDB and CSF Alzheimer's disease-biomarkers in cognitively normal elderly individuals. Existing therapies for SDB such as continuous positive airway pressure could delay the onset to mild cognitive impairment or dementia in normal elderly individuals.

摘要

以往研究表明睡眠呼吸紊乱(SDB)与痴呆风险之间存在联系。在本研究中,我们分析了SDB严重程度、脑脊液(CSF)阿尔茨海默病生物标志物和载脂蛋白E(ApoE)等位基因之间的关系。共对95名认知正常的老年参与者进行了SDB严重程度、磷酸化tau蛋白(p-tau)、总tau蛋白(t-tau)和淀粉样β蛋白42(Aβ-42)的脑脊液检测,以及ApoE等位基因状态分析。在携带ApoE3的受试者中,睡眠组之间的p-tau(F[自由度2]=4.3,p=0.017)和t-tau(F[自由度2]=3.3,p=0.043)存在显著差异。此外,在携带ApoE3的受试者中,伴有4%氧饱和度下降指数的呼吸暂停和/或呼吸不足与p-tau(r=0.30,p=0.023)、t-tau(r=0.31,p=0.021)和Aβ-42(r=0.31,p=0.021)呈正相关。在携带ApoE2的受试者中,伴有4%氧饱和度下降指数的呼吸暂停和/或呼吸不足与脑脊液Aβ-42水平较低相关(r=-0.71,p=0.004),与携带ApoE4的受试者情况类似,后者脑脊液Aβ-42水平也有降低趋势。我们的观察结果表明,在认知正常的老年人中,SDB与脑脊液阿尔茨海默病生物标志物之间存在关联。现有的SDB治疗方法,如持续气道正压通气,可能会延缓正常老年人出现轻度认知障碍或痴呆的时间。

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