Dataset Information

Interleukin-1? Promoter Polymorphism Enhances the Risk of Sleep Disturbance in Alzheimer's Disease.

ABSTRACT: Sleep alleviates Alzheimer's disease (AD)-related neuropathological processes, whereas sleep disturbance in AD patients is associated with elevated peripheral inflammatory cytokine levels. In the present study, we assessed interleukin (IL)-1? and APOE?4 polymorphisms for association with susceptibility of sleep disturbances in AD patients. A total of 123 pretreated AD patients and 120 age-, gender- and education level-matched healthy controls were recruited for two consecutive full-night polysomnography and measurement of Epworth Sleepiness Scale (ESS) scores for sleep-wake disturbance. Their genomic DNA was analyzed for IL-1? and APOE?4 SNPs using ligase detection reaction (LDR) technology. Blood levels of IL-1?, IL-6, and tumor necrosis factor alpha (TNF-?) were measured using ELISA after lipopolysaccharide (LPS) stimulation. The odds ratio and 95% confidence interval for genotype-specific risk were calculated using an unconditional logistic regression model and adjusted by age, gender, educational levels, body mass index (BMI), and activities of daily living (ADL). Compared to the non-APOE?4/?4 genotype, APOE?4/?4 significantly increased the risk of AD (APOE?4/?4 vs. non-APOE?4/?4, adjusted OR = 4.33, 95% CI = 1.33-14.10, p = 0.015). Compared to the IL-1? CC genotype (-31), the TT genotype significantly increased the risk of AD (TT vs. CC, adjusted OR = 1.72, 95% CI = 1.13-2.61, p = 0.010). AD patients carrying the APOE?4 allele and the IL-1? TT genotype showed less time in bed, longer sleep latency and REM latency, more awakenings, and a lower SWS percentage than those carrying CC/CT combined genotypes. In addition, blood IL-1? levels were significantly greater in AD patients carrying both the APOE?4 allele and the IL-1?-31TT genotype than in those carrying the APOE?4 allele and the -31 TC or CC genotype. In conclusion, this study provides the first evidence indicating that the IL-1?-31TT genotype and homozygous APOE?4 combined are associated with increased risk of developing AD with sleep disturbance.

SUBMITTER: Yin Y

PROVIDER: S-EPMC4777499 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Interleukin-1β Promoter Polymorphism Enhances the Risk of Sleep Disturbance in Alzheimer's Disease.

Yin You Y Liu Yan Y Pan Xiao X Chen Rui R Li Peng P Wu Hui-Juan HJ Zhao Zheng-Qing ZQ Li Yan-Peng YP Huang Liu-Qing LQ Zhuang Jian-Hua JH Zhao Zhong-Xin ZX

PloS one 20160303 3

Sleep alleviates Alzheimer's disease (AD)-related neuropathological processes, whereas sleep disturbance in AD patients is associated with elevated peripheral inflammatory cytokine levels. In the present study, we assessed interleukin (IL)-1β and APOEε4 polymorphisms for association with susceptibility of sleep disturbances in AD patients. A total of 123 pretreated AD patients and 120 age-, gender- and education level-matched healthy controls were recruited for two consecutive full-night polysom ...[more]

PMID: 26937653

Similar Datasets

Project description:BackgroundApolipoprotein E epsilon 4 (APOE-ε4) carrier status is an established risk factor for Alzheimer's disease (AD) dementia. It has also been linked with sleep disturbance in healthy older adults and increased insomnia risk. This association may be driven by the effect of APOE-ε4 on AD pathological change, itself associated with sleep abnormalities. To assess this relationship, we have evaluated post-mortem neuropathological findings in patients with and without cognitive impairment and AD pathology, who had extensive clinical assessment within 12 months of death.MethodsThis retrospective cohort study used UK Brain Banks Network data. Eligible subjects were aged over 50, with pre-mortem neuropsychiatry inventory scores of sleep disturbance (NPI-K), neurocognitive testing and functional cognitive status assessment (Clinical Dementia Rating scale). Neuropathological data included Thal phase, Braak stage and CERAD scores (measures of Aβ plaque distribution, tangle distribution and neuritic plaque density, respectively) combined to form the National Institute on Aging Alzheimer's Association (NIA-AA) ABC score reflecting AD neuropathology. Participants with other significant intracerebral pathology or pathological features of non-AD dementia were excluded. Multivariate linear regression was performed with NPIK Global Score (NPIK frequency score multiplied by severity score) as the dependent variable and APOE-ε4 heterozygosity or homozygosity as independent variables. Covariates included age, gender, APOE-ε2 status and ABC NPI measures reflecting depression and anxiety. Further models stratified by ABC score and functional cognitive status were also produced.ResultsSeven hundred twenty-eight records were identified. Two hundred two participants were included in the final analysis: mean (SD) age 84.0 (9.2) and MMSE 14.0 (11.8). Mean sleep disturbance scores were highest in ε4 homozygosity (n=11), 4.55 (5.4); intermediate in ε4 heterozygosity (n=95), 2.03 (4.0); and lowest in non-ε4 carriers (n=96), 1.36 (3.3). Within the full sample, controlling for pathological status, age, gender, depression, anxiety and CDR-SOB status, APOE-ε4 homozygosity was associated with sleep disturbance (β 2.53, p=0.034). APOE-ε4 heterozygosity was similarly associated in individuals without dementia (β 1.21, p=0.048).ConclusionThese findings lend weight to the hypothesis that APOE-ε4 affects sleep by mechanisms independent of AD pathological change. Evaluation of those mechanisms would enhance understanding of sleep disturbance pathways and potentially provide treatment targets.

Dataset Information

Interleukin-1? Promoter Polymorphism Enhances the Risk of Sleep Disturbance in Alzheimer's Disease.

Publications

Interleukin-1β Promoter Polymorphism Enhances the Risk of Sleep Disturbance in Alzheimer's Disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets