Symptomatic Alzheimer's disease (AD) has been associated with a cortical signature of thinning in specific limbic and association regions (Bakkour et al. 2009, Dickerson et al. 2009) measured with MRI. In this study we investigated whether the cortical signature of AD-related thinning is present in Presenilin 1 (PS1) E280A mutation carriers, an average of 7 years before clinical onset (mean age of45). Thirty-nine volunteers from a Colombian population with familial AD were included. Eighteen presymptomatic subjects were positive for the Alzheimer's-associated PS1 mutation (carriers) whereas 21 were non-carriers. Subject groups were matched for age, sex, education, and performance on the CERAD cognitive battery. T1-weighted volumetric MRI images were acquired using a Philips 1.5 T MRI scanner. Cortical thickness was measured in a fully automated fashion using FreeSurfer. A priori regions of interest (ROIs) were used to obtain thickness from “AD-signature regions”, identified previously in mild AD dementia patients. ANOVA was used to compare the groups using the entire summary measure as well as individual regions. The presymptomatic PS1mutation carriers and non-carriers did not differ significantly in their age (37±6 years), gender (78% female), educational level (11±2 years), or MMSE scores (29±0.8). Compared to noncarriers, presymptomatic PS1 carriers showed cortical thinning in the AD-signature summary measure (p< 0.008). Analyses of individual signature ROIs demonstrated thinning in right angular gyrus, right precuneus and left superior parietal lobule in carriers compared to non-carriers (p<0.05, uncorrected for multiple comparisons). Cognitively normal individuals at genetic risk for early-onset AD have subtle cortical thinning in brain regions known to be affected by typical late-onset sporadic AD. Further research is needed to determine whether this method could be used to characterize the age-dependent trajectory of atrophy in these and other brain regions in presymptomatic PS1 carriers and support their use in the evaluation of presymptomatic AD treatments.