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P4‐108: Beta‐amyloid reduces the expression of antioxidant repair genes
Author(s) -
Duran Jorge,
PerezCordova Miriam,
PachecoOtalora Luis,
Perry George,
Colom Luis
Publication year - 2012
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2012.05.1811
Subject(s) - sod1 , superoxide dismutase , oxidative stress , hippocampus , neurodegeneration , amyloid beta , medicine , endocrinology , gene expression , hippocampal formation , biology , gene , biochemistry , disease
ical AD are unknown. We aimed to assess whether known risk factors for typical AD were shared with PCA; to compare the effect sizes at these loci; and for the first time to explore genome-wide for loci conferring very strong genetic risk for PCA. Methods: We performed a pilot GWAS in a small but carefully defined single-center case series of patients with PCA (n 1⁄4 58), using Genetic and Environmental Risk for Alzheimer’s disease (GERAD1) Consortium controls (n 1⁄4 1217) as comparators. We compared APOE E4 carrier frequency in the PCA group with that from 198 patients with typical amnestic AD. Results: Although the APOE E4 carrier frequency was slightly lower in PCA (0.45) than typical AD (0.55), this difference was not significant. At the other known risk loci, the central estimates of effect sizes were generally less strong or opposite from those reported in typical AD, with the notable exception of rs3764650 at ABCA7 (OR 1.88, 95% CI 1.08-3.27) where the effect size was similar to APOE. Whilst no genome-wide significant loci were found, more (n 1⁄4 17) SNPs achieved P<10 -5 than would be expected (n1⁄4 5). Conclusions: Clinical variants and early onset AD provide an opportunity to study genetic modifiers of phenotype by minimizing heterogeneity. The ABCA7 finding if replicated may relate to the distinct phenotype of PCA and/or relatively early age-at-onset. It is hoped that these pilot data will stimulate the ascertainment of larger case series and combined GWAS.