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• W2029879907 abstract "Apolipoprotein E (ApoE) genotype is a major risk factor for Alzheimer disease (AD), but the underlying mechanism for this effect remains uncertain. Our previous work demonstrated that ApoE genotype modulates levels of multiple plasma proteins in a small cohort of young subjects with and without early-onset autosomal dominant AD mutations. Based on these findings, we sought to determine whether similar ApoE genotype dependent changes in plasma protein levels were present in the elderly cohort of subjects included in the Alzheimer's Disease Neuroimaging Initiative (ADNI) plasma biomarkers project. EDTA plasma samples were obtained from the young UCLA [mean age = 35.0 (SD = 10.3); N = 33] and elderly ADNI [mean age = 74.8 (SD = 7.4); N = 566] cohorts, which both contained subjects with normal cognition, mild cognitive impairment, and AD. Samples were analyzed with a 77-analyte multiplex immunoassay panel on the Luminex xMAP platform by Rules-Based Medicine. Results from 56 analytes were determined to be statistically reliable and included in further analyses. For each protein, separate analyses of covariance were performed for each cohort, comparing between ApoE genotypes and covarying for age. Significant differences were seen between young and elderly cohorts for 45 of 56 proteins analyzed, suggesting that plasma protein levels are highly age-dependent. In both the young and elderly cohorts, significant ApoE genotype effects were seen for ApoE (E2 > E3 > E4) and IL-13 (E4 and E3 > E2). In the young cohort, additional significant ApoE genotype effects were seen for AXL receptor tyrosine kinase (E3 > E2), BDNF (E2 > E3 and E4), CD5 antigen-like (E4 > E3), chromogranin A (E3 > E2), EGF (E2 > E3), I-309 (E4 > E2), IL-3 (E3 and E4 > E2), MIP-1b (E2 > E3), RANTES (E2 > E3), and SOD-1 (E2 > E3 and E4). In the elderly cohort, additional significant ApoE genotype effects were seen for ApoB (E3 and E4 > E2) and ApoD (E2 > E3 and E4). Our results indicate that ApoE genotype modulates levels of multiple plasma proteins, including apolipoproteins, inflammatory mediators, trophic factors, and anti-oxidants. A larger number of ApoE genotype related differences in protein levels were seen in the young cohort than in the elderly cohort. These findings support the hypothesis that ApoE genotype influences AD risk through multiple mechanisms that are most prominent at early to mid-adulthood." @default.
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• W2029879907 date "2011-07-01" @default.
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• W2029879907 title "P1-120: APOE genotype differences in plasma protein levels in young and elderly cohorts" @default.
• W2029879907 doi "https://doi.org/10.1016/j.jalz.2011.05.400" @default.
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