Associations between Certain Polymorphisms in Proinflammatory Cytokines and Predisposition of Alzheimer’s Disease: A Meta-Analysis

Zhang, Qin; Yang, Kongbin; Zhang, ZhongLing; Zhang, Ruihua

doi:10.1159/000508889

Cited by 6 publications

(6 citation statements)

References 19 publications

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“…In our study, CSF IL-6 did not correlate with CSF AD biomarkers (Spearman’s rho = 0.053, p = 0.4 for Aβ42; Spearman’s rho = −0.014, p = 0.829 for p-tau; and Spearman’s rho = −0.05, p = 0.427 for Aβ42/p-tau). It appears that the relationship between IL-6, AD and neurodegeneration depend on other pro-inflammatory and anti-inflammatory cytokines and different endophenotypic expression of inflammatory markers ( Wang et al, 2015 ; Peng et al, 2020 ), in addition to IL-6 receptor polymorphisms ( Su et al, 2016 ; Haddick et al, 2017 ; Zhang et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Sleepiness in Cognitively Unimpaired Older Adults Is Associated With CSF Biomarkers of Inflammation and Axonal Integrity

Carvalho

Louis

Przybelski

et al. 2022

Front. Aging Neurosci.

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IntroductionSleepiness has been associated with cognitive decline and dementia in the elderly. Older adults with excessive daytime sleepiness appear to be more vulnerable to longitudinal amyloid PET accumulation before the onset of the dementia. However, it remains unclear whether sleepiness is similarly associated with other biomarkers of Alzheimer’s disease (AD), axonal integrity, and inflammation, which may also contribute to neurodegeneration and cognitive decline.MethodsIn this cross-sectional analysis, we identified 260 cognitively unimpaired adults (>60 years) from the Mayo Clinic Study of Aging, a population-based cohort from Olmsted County (MN), who underwent CSF quantification of AD biomarkers (Aβ42, p-tau, p-tau/Aβ42) in addition to at least one of the following biomarkers [neurofilament light chain (NfL) interleukin-6 (IL-6), IL-10, and tumor necrosis factor-α (TNF-α)]. We fit linear regression models to assess associations between sleepiness, as measured by the Epworth Sleepiness Scale (ESS), and CSF biomarkers, controlling for age, sex, APOε4 status, body mass index, hypertension, dyslipidemia, and prior diagnosis of obstructive sleep apnea.ResultsHigher ESS scores were associated with higher CSF IL-6 and NfL, but not with the other CSF biomarkers. For every ESS score point increase, there was a 0.009 ([95% CI 0.001–0.016], p = 0.033) increase in the log of IL-6 and 0.01 ([95% CI 0.002–0.018], p = 0.016) increase in the log of NfL. A sensitivity analysis showed an association between ESS scores and log of p-tau/Aβ42 only in participants with an abnormal ratio (>0.023), highly predictive of amyloid positivity. For every ESS score point increase, there was a 0.006 ([95% CI 0.001–0.012], p = 0.021) increase in the log of CSF p-tau/Aβ42.ConclusionSleepiness was associated with greater CSF IL-6 and NfL levels, which could contribute to neurodegeneration or alternatively cause sleepiness. Higher NfL levels may result from sleep disruption and/or contribute to sleepiness via disturbed connectivity or damage to wake-promoting centers. Associations between sleepiness and p-tau/Aβ42 in participants with abnormal ratio suggest that amyloid positivity contributes to vulnerability to sleep disturbance, which may further amyloid accumulation in a feed-forward loop process. Prospective studies of these markers are needed to determine cause-effect relationships between these associations.

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Section: Discussionmentioning

confidence: 99%

Sleepiness in Cognitively Unimpaired Older Adults Is Associated With CSF Biomarkers of Inflammation and Axonal Integrity

Carvalho

Louis

Przybelski

et al. 2022

Front. Aging Neurosci.

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“…In contrast, Zhang et al, (2019) found a significant association between the rs4073 A allele increasing coronary artery disease (CAD) risk in a Chinese population, but this association was not observed in Caucasians [384]. Zhang et al, (2021) conducted a meta-analysis revealing that CXCL8 rs4073 polymorphisms may affect a predisposition to Alzheimer's disease in people who are Asian, but not in people who are Caucasian [198]. This suggests that CXCL8 gene polymorphism can have a distinct influence not only on various disease states but also on health outcomes across diverse populations.…”

Section: Discussionmentioning

confidence: 99%

“…Nonetheless, another study found no interactive effect between the rs4073 and IL-1α -889C/T (rs1800587) polymorphisms in patients with AD [197]. Furthermore, meta-analyses of the rs4073 polymorphism suggested a possible predisposition to AD in individuals of Asian ethnicity [198,199].…”

Section: Cxcl8 Gene and Snpsmentioning

confidence: 99%

IL-8 (CXCL8) Correlations with Psychoneuroimmunological Processes and Neuropsychiatric Conditions

Shkundin,

Halaris

2024

JPM

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Interleukin-8 (IL-8/CXCL8), an essential CXC chemokine, significantly influences psychoneuroimmunological processes and affects neurological and psychiatric health. It exerts a profound effect on immune cell activation and brain function, suggesting potential roles in both neuroprotection and neuroinflammation. IL-8 production is stimulated by several factors, including reactive oxygen species (ROS) known to promote inflammation and disease progression. Additionally, CXCL8 gene polymorphisms can alter IL-8 production, leading to potential differences in disease susceptibility, progression, and severity across populations. IL-8 levels vary among neuropsychiatric conditions, demonstrating sensitivity to psychosocial stressors and disease severity. IL-8 can be detected in blood circulation, cerebrospinal fluid (CSF), and urine, making it a promising candidate for a broad-spectrum biomarker. This review highlights the need for further research on the diverse effects of IL-8 and the associated implications for personalized medicine. A thorough understanding of its complex role could lead to the development of more effective and personalized treatment strategies for neuropsychiatric conditions.

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“…In addition to RA predisposition, increasing evidence on the association between IL-18 polymorphisms and other disease conditions has also been reported by systematic reviews and meta-analyses. The -607 C/A and/or -137 G/C polymorphisms in IL-18 may confer susceptibility to tuberculosis, especially in Asians [33]; inflammatory bowel disease, including both Crohn's disease and ulcerative colitis in Asians and Africans [34][35][36]; vasculitis [37] and systemic lupus erythematosus in Europeans and Asians [38]; Behcet's disease [39], various types of liver diseases [40,41], hepatitis B virus in East Asians and hepatitis C virus infection in South Asians [42] and Asian populations [43]; diabetic nephropathy in Asians [44]; allergic asthma and allergic dermatitis [45][46][47], Alzheimer's disease in Asians [48,49]; periodontitis [50], coronary artery disease in East Asians [51,52]; head and neck cancer risk, especially nasopharyngeal cancer, in Asian populations [53]; breast cancer in East Asians from China [54,55]; and prostate cancer in Asian and Caucasian populations [56]. IL-18 has been reported to be a potential clinical biomarker.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-18 Gene Polymorphisms and Rheumatoid Arthritis Susceptibility: An Umbrella Review of Meta-Analyses

Chen,

Ye,

Liu

et al. 2024

Journal of Immunology Research

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This study systematically analyzes the association between interleukin-18 (IL-18) gene polymorphisms and rheumatoid arthritis (RA) susceptibility. The electronic databases Ovid MEDLINE, Ovid Excerpta Medica Database, and Cochrane Library were searched to identify meta-analyses that included case–control studies reporting IL-18 gene polymorphisms and RA susceptibility. Data were reanalyzed using Review Manager Software 5.1, and Mantel–Haenszel random effects were applied for the five genetic models: allelic, recessive, dominant, homozygote, and heterozygote. The effect size of odds ratios (ORs) and their corresponding 95% confidence interval (CI) were calculated. A total of seven meta-analyses with poor quality were included. The IL-18 polymorphisms -607 A/C, -137 C/G, -920 T/C, and -105 C/A have been reported. With weak evidence, IL-18 -607 A/C polymorphisms were associated with a reduced risk of RA susceptibility using the allele model (OR = 0.76, 95% CI: 0.61 − 0.93, p=0.01), dominant model (OR = 0.67, 95% CI: 0.50 − 0.90, p=0.008), homozygote model (OR = 0.57, 95% CI: 0.35 − 0.91, p=0.02), and heterozygote model (OR = 0.71, 95% CI: 0.54 − 0.93, p=0.01) in the overall population. IL-18 gene polymorphisms and RA susceptibility are affected by ethnicity: With weak evidence, IL-18 -137 C/G polymorphisms were related to reduce RA susceptibility in the Asian population (allele model: OR = 0.59, 95% CI: 0.40 − 0.88, p=0.01; dominant model: OR = 0.57, 95% CI: 0.37 − 0.89, p=0.01; heterozygote model: OR = 0.60, 95% CI: 0.38 − 0.94, p=0.03). IL-18 -607 A/C gene polymorphisms are a protective factor for RA susceptibility in the overall population, and IL-18 −137 C/G gene polymorphisms are a protective factor for RA susceptibility in the Asian population. Further studies are needed to confirm these results owing to the limitations of the included studies.

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Associations between Certain Polymorphisms in Proinflammatory Cytokines and Predisposition of Alzheimer’s Disease: A Meta-Analysis

Cited by 6 publications

References 19 publications

Sleepiness in Cognitively Unimpaired Older Adults Is Associated With CSF Biomarkers of Inflammation and Axonal Integrity

Sleepiness in Cognitively Unimpaired Older Adults Is Associated With CSF Biomarkers of Inflammation and Axonal Integrity

IL-8 (CXCL8) Correlations with Psychoneuroimmunological Processes and Neuropsychiatric Conditions

Interleukin-18 Gene Polymorphisms and Rheumatoid Arthritis Susceptibility: An Umbrella Review of Meta-Analyses

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