Interleukin-6 gene alleles affect the risk of Alzheimer's disease and levels of the cytokine in blood and brain
Abstract
Two different polymorphic regions of the interleukin-6 (IL-6) gene were investigated in patients with Alzheimer's disease (AD) and non-demented controls. The -174 C allele in the promoter region of IL-6 gene was over-represented in AD patients compared to controls and significantly increased the risk of AD. Moreover, the -174 CC genotype was associated with a high risk of the disease in women. The D allele of a variable number of tandem repeat (VNTR) was in strong linkage disequilibrium with the -174 C allele and slightly increased AD risk. On the other hand, the frequency of the VNTR C allele was decreased in patients with AD and was negatively associated with the risk of developing AD. Both the -174 CC and VNTR DD genotypes were also associated with increased IL-6 levels in the blood and brain from AD. These findings suggest that IL-6 may play a multifaceted role in AD by affecting the turnover of the cytokine.
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Prior work linked the -174C allele to elevated brain IL6 levels.
“the - 174C allele was previously associated with higher levels of IL6 in the brain (Licastro, et al., 2003).”
From A potential endophenotype for Alzheimer's disease: cerebrospinal fluid clusterin (2016) · cites this paper as Licastro, et al., 2003
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- Authors
- Licastro, F., Grimaldi, L. M. E., Bonafè, M., Martina, C., Olivieri, F., Cavallone, L., Giovanietti, S., Masliah, E., & Franceschi, C.
- Affiliations
- University of Bologna (IT)
- University of California San Diego (US)
- Corresponding author
- Licastro, Federico
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2003-11
- Volume
- 24
- Issue
- 7
- Pages
- 921-926
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2058795549
- Cited by
- 182
- References
- 39
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 3 · 2023: 1 · 2022: 6 · 2021: 6 · 2020: 8 · 2019: 7 · 2018: 4 · 2017: 5 · 2016: 6 · 2015: 5 · 2014: 5 · 2013: 7 · 2012: 6
- FWCI
- 9.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (P50AG005131, AG-5131)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- interleukin-6, Alzheimer's disease, genetic polymorphism, promoter polymorphism, variable number tandem repeats, linkage disequilibrium, disease risk, sex differences, cytokine levels, blood, brain, genetic susceptibility
- MeSH terms
- Aged, Aging, Alzheimer Disease, Analysis of Variance, Apolipoproteins E, Female, Frontal Lobe, Gene Frequency, Humans, Italy, Male, Middle Aged, Polymorphism, Genetic, Promoter Regions, Genetic, Reference Values, Risk Factors, Sex Factors, Linkage Disequilibrium, Interleukin-6, Minisatellite Repeats, Genetic Predisposition to Disease, 3' Flanking Region, Apolipoprotein E4
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