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• W2897069696 abstract "Peripheral inflammatory burden has been associated with increased risk of many debilitating diseases. Specific inflammatory biomarkers such as interleukins, C-reactive protein and TNFα have been identified by several research groups as being associated with increased risk of Alzheimer's Disease (AD). In the current study, we investigated modulation of AD risk by combining a targeted selection of ∼2000 AD-associated single nucleotide polymorphisms (SNPs) with a novel inflammatory index, using data from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study. A panel of 18 biomarkers from the Rules Based Medicine platform, measured on the baseline AIBL dataset, were used to derive a peripheral inflammatory burden score, with a value of one for each biomarker assigned to either cognitively normal (CN) or AD participants who had a value in the top 20% of the risk range. The score was then summed (total score range 0-18) and converted to a binary factor, with individuals scoring less than the mean value (3.6) assigned a ‘zero’, and those with a score of four or more assigned a ‘one’. These data were then analysed in the presence/absence of at least one polymorphic allele for each of the ∼2000 SNPs to evaluate AD risk, i.e. CN-vs-AD. Through assessing the interaction between SNP and peripheral inflammatory burden score for the risk of AD, we identified 41 SNPs from 29 individual genes (top genes included CYP11B2 (rs6438- OR: 4.91 [95%CI: 2.69 – 8.96], p=2.31*10−7), HSD3B2 (rs12411080- OR: 5.0 [95%CI: 2.67 – 9.35], p=5.01*10−7) and APOC1 (rs4420638- OR: 4.89 [95%CI: 2.63 – 9.1], p=5.36*10−7)) with significant (p<2.5*10−5) interactions associated with AD. The remaining SNPs in combination with a peripheral inflammatory burden score of at least 4 had similar increases in risk for AD; of note were six SNPs in the CYP11B2 gene, three in the FYCO1 gene, and three in the ACO1 gene. Measurable peripheral inflammatory burden risk factors in combination with known AD-related SNPs appear to demonstrate modulation of AD risk. Further investigation is required to determine the prognostic utility of such an approach." @default.
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• W2897069696 date "2018-07-01" @default.
• W2897069696 modified "2023-10-16" @default.
• W2897069696 title "P1‐142: PERIPHERAL INFLAMMATORY BURDEN BIOMARKERS MODULATE THE RISK FOR ALZHEIMER'S DISEASE THROUGH KEY AD‐RELATED SNPS" @default.
• W2897069696 doi "https://doi.org/10.1016/j.jalz.2018.06.145" @default.
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