Cytokine IL‐1 beta but not IL‐1 alpha promoter polymorphism is associated with Alzheimer disease in a population from the Canary Islands, Spain

Deniz-Naranjo, M. Candida; Muñoz-Fernández, Carmen; Alemany-Rodríguez, M J; Pérez-Vieitez, M. C.; Aladro-Benito, Yolanda; Irurita-Latasa, J.; Sánchez-García, Florentino

doi:10.1111/j.1468-1331.2008.02252.x

Cited by 40 publications

(27 citation statements)

References 29 publications

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“…138,139 In one study, IL1B at -511 increased the odds for AD but the IL1A -889 polymorphism did not. 140 A strong association was shown between AD and IL1B +3954, but not -511 in another study. 141 Other studies have found no relation between IL1B-511 and AD.…”

Section: Interleukin-1mentioning

confidence: 97%

Neuroinflammatory Cytokines—The Common Thread in Alzheimer Pathogenesis

Griffin¹,

Barger²

2010

US Neurology

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This article discusses the potential role of the cytokine cycle and its corollary as drivers of the relentless progression of Alzheimer's neuropathologies, whether they are the result of gene mutations, gene polymorphisms, and/or environmental and comorbid conditions. Based on the discovery of cytokine overexpression as an accompaniment to the dementia-related glial activation, the cytokine hypothesis wasproposed. This states that in response to the negative impact on neurons of known and unknown risk factors-which include genetic inheritance, comorbid and environmental factors-microglia and astrocytes become activated and produce excess amounts of the immune-modulating cytokine interleukin-1 (IL-1) and the neuritogenic cytokine S100B, respectively. Finding that these glial events occur in fetuses and neonates with Down syndrome provided the first evidence that productive immune responses by activated glia precede rather than follow overt AD-related pathology. This finding can be added to the demonstration of IL-1 induction of amyloid β (Aβ) precursor protein and astrocyte activation with excess production of neuritogenic factor S100B. This combination suggests that IL-1 and S100B overexpression would favor the Aβ production and dystrophic neurite growth necessary for laying down neuritic Aβ plaques. This, together with demonstration of IL-1 induction of excessive production of the precursors of other features common in AD prompted a corollary to the cytokine hypothesis. The corollary states that regardless of the primary cause of the neuronal insult, the result will be chronic glial activation, which in turn will result in further neuronal injury, still more glial activation with excess cytokine expression and so on. This article discusses known causes, genetic and environmental risk factors, and comorbid conditions, and the potential contribution of glial activation with excessive cytokine expression to each. KeywordsAlzheimer's disease (AD), amyloid β (Aβ), apolipoprotein E (ApoE), β−amyloid precursor protein (βAPP), cytokines, Down syndrome (DS), excitotoxicity, glutamate, interleukin-1 (IL-1), S100B, tumor necrosis factor alpha (TNFα) Disclosure: The authors have no conflicts of interest to declare. Acknowledgments:Much of the work cited in this article was supported by National Institutes of Health (NIH) grants P01AG12411 (to WSTG) and R01AG17498 (to SWB). The authors thank Orwa Aboud, MD, for helpful comments and editing. A progression of these neuropathological events seems apparent. For example, the plethora of Aβ plaques at end stages-from several to many-and an inclusion of neurofibrillary tangles-in a few to numerous neurons-strongly suggests that these neuropathological Received

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Section: Interleukin-1mentioning

confidence: 97%

Neuroinflammatory Cytokines—The Common Thread in Alzheimer Pathogenesis

Griffin¹,

Barger²

2010

US Neurology

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“…This meta-analysis proved that there is a need for future studies to confirm or exclude an association between the -511 CT polymorphism and AD. Shortly after the publication of this meta-analysis, a study on 282 Caucasian AD cases and 312 controls brought positive results regarding the association between the IL-1 ␤ -511 polymorphism and AD [14] . Meta-analysis of 16 studies with Caucasian patients on rs3087258 SNP (-511, allele T versus C effect) included in AlzGene database (http://www.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-1 Gene –511 CT Polymorphism and the Risk of Alzheimer’s Disease in a Polish Population

Klimkowicz-Mrowiec

Marona²,

Wołkow³

et al. 2009

Dement Geriatr Cogn Disord

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Interleukin-1 is a potent proinflammatory cytokine involved in the pathophysiology of Alzheimer’s disease (AD). We genotyped IL-1β (–511 C/T) and the apolipoprotein E (APOE) common polymorphisms in a large case-controlled study in a Polish population. We included 332 patients with late-onset AD and 220 controls without any neurological deficit, cognitive complaints and history of neurological diseases, aged ≥ 65 years. The distribution of the IL-1β (–511 C/T) genotypes was similar to that in the controls (AD: C/C = 45.8%, C/T = 44.6%, T/T = 9.6% vs. controls: C/C = 53.9%, C/T = 38.3%, T/T = 7.3%, p > 0.05). Our study confirms previous reports that APOE ε4 is strongly related to the risk of AD (odds ratio = 6.60, 95% confidence interval 4.19–10.41). APOE status did not affect the distribution of the studied IL-1β polymorphism. The IL-1β (–511 C/T) polymorphism is not a risk factor for late-onset AD in a Polish population.

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“…Indeed, previous studies demonstrated overexpression of IL-1 ␤ in the brain of AD patients [11,12] . Moreover, IL-1 ␤ polymorphisms responsible for higher production of the cytokine were also associated with an increased risk for AD [13,14] .…”

Section: Introductionmentioning

confidence: 99%

Increased Serum IL-1β Level in Alzheimer’s Disease and Mild Cognitive Impairment

Forlenza

Diniz

Talib

et al. 2009

Dement Geriatr Cogn Disord

187

103

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Background/Aims: Abnormal inflammatory response has been associated to the pathogenesis of Alzheimer’s disease (AD) and may be a marker of an ongoing neurodegenerative process. The aim of this study was to evaluate the serum levels of interleukin-1β (IL-1β) in patients with mild cognitive impairment (MCI) and AD. Methods: One hundred and sixty-three older adults (58 with mild to moderate AD, 74 with MCI and 31 healthy controls) were recruited for this study. Serum IL-1β levels were measured by ELISA. Patients with MCI were subcategorized in single-domain amnestic (aMCI), nonamnestic (naMCI), and multiple-domain (mdMCI) subtypes. Results: Patients with AD and MCI (all subtypes) had a significant increase in serum IL-1β levels as compared to controls (p = 0.03). Patients with mdMCI had serum IL-1β levels comparable to those with AD, and significantly higher than those observed in aMCI and naMCI (p = 0.02). Discussion: The present study provides evidence that inflammatory mechanisms, represented by elevated IL-1β, are observed in patients with MCI, specifically in those with impairment in multiple cognitive domains. As these patients are at higher risk of conversion to dementia, we propose that an increased serum IL-1β level is a stage marker of the ongoing brain neurodegeneration in the continuum between normal ageing and AD.

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Cytokine IL‐1 beta but not IL‐1 alpha promoter polymorphism is associated with Alzheimer disease in a population from the Canary Islands, Spain

Abstract: In our population, IL-1 beta promoter polymorphism (-511 C/T) is an independent risk factor for AD.

Cited by 40 publications

References 29 publications

Neuroinflammatory Cytokines—The Common Thread in Alzheimer Pathogenesis

Neuroinflammatory Cytokines—The Common Thread in Alzheimer Pathogenesis

Interleukin-1 Gene –511 CT Polymorphism and the Risk of Alzheimer’s Disease in a Polish Population

Increased Serum IL-1β Level in Alzheimer’s Disease and Mild Cognitive Impairment

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