Genetic risks of Alzheimer's by and on cortical morphology in young healthy adults.

Genetic risk factors such as ε4 and (rs242557) A allele are associated with amyloid and tau pathways and grey matter changes at both early and established stages of Alzheimer's disease, but their effects on cortical morphology in young healthy adults remain unclear. A total of 144 participants aged from 18 to 24 underwent 3T MRI and genotyping for and to investigate unique impacts of these genetic risk factors in a cohort without significant comorbid conditions such as metabolic and cardiovascular diseases. We segmented the cerebral cortex into 68 regions and calculated the cortical area, thickness, curvature and folding index for each region. Then, we trained machine learning models to classify and genotypes using these morphological features. In addition, we applied a growing hierarchical self-organizing maps algorithm, which clustered the 68 regions into 4 subgroups representing different morphological patterns. Then, we performed general linear model analyses to estimate the interaction between and on cortical patterns. We found that the classifiers using all cortical features could accurately classify individuals carrying genetic risks of dementia outperforming each individual feature alone. ε4 carriers had a more convoluted and thinner cortex across the cerebral cortex. A similar pattern was found in A allele carriers only in the regions that are vulnerable for early tau pathology. With the clustering analysis, we found a synergetic effect between ε4 and A allele, i.e. carriers of both risk factors showed the most deviation of cortical pattern from the typical pattern of that cluster. Genetic risk factors of dementia by ε4 and (rs242557) A allele were associated with variations of cortical morphology, which can be observed in young healthy adults more than 30 years before Alzheimer's pathology is likely to occur and 50 years before dementia symptoms may begin.