Gene-brain structure associations of 3 recently discovered risk genes for Alzheimer's disease, CLU (rs11136000C>T), CR1 (rs6656401G>A), and PICALM (rs3851179G>A), were investigated in 2 independent cohorts of young healthy adults (n = 430 and n = 492, respectively). We assessed structural differences in 2 core structures of Alzheimer pathology, entorhinal cortex and hippocampus, by voxel-based morphometry using high-resolution magnetic resonance imaging (MRI) data. For CLU and PICALM no significant genotype-related differences in local gray matter volume were found. CR1 risk allele (A) carriers showed smaller local gray matter volume in the entorhinal cortex, as confirmed in both cohorts. This association, apparent in young healthy adults, might mediate susceptibility for Alzheimer's disease later in life.
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