Differential default mode network trajectories in asymptomatic individuals at risk for Alzheimer's disease

Abstract Introduction The longitudinal trajectories of functional brain dynamics and the impact of genetic risk factors in individuals at risk for Alzheimer's disease are poorly understood. Methods In a large-scale monocentric cohort of 224 amyloid stratified individuals at risk for Alzheimer's disease, default mode network(DMN) resting state functionalconnectivity (FC) was investigated between two serial time points across 2 years. Results Widespread DMN FC changes were shown in frontal and posterior areas, as well as in the right hippocampus. There were no cross-sectional differences, however, apolipoprotein Ee4 ( APOE e4) carriers demonstrated slower increase in FC in frontal lobes. There was no impact of individual brain amyloid load status. Discussion For the first time, we demonstrated that the pleiotropicbiological effect of the APOE e4 allele impacts the dynamic trajectory of the DMN during aging. Dynamic functional biomarkers may become useful surrogate outcomes for the development of preclinical targeted therapeutic interventions.