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

Chiesa, P. A.; Cavedo, E.; Vergallo, A.; Lista, S.; Potier, M. -C.; Habert, M. -O.; Dubois, B.; Thiebaut de Schotten, M.; Hampel, H.; Audrain, C.; Auffret, A.; Bakardjian, H.; Baldacci, F.; Batrancourt, B.; Benakki, I.; Benali, H.; Bertin, H.; Bertrand, A.; Boukadida, L.; Cacciamani, F.; Causse, V.; Cavedo, E.; Cherif Touil, S.; Chiesa, P. A.; Colliot, O.; Dalla Barba, G.; Depaulis, M.; Dos Santos, A.; Dubois, B.; Dubois, M.; Epelbaum, S.; Fontaine, B.; Francisque, H.; Gagliardi, G.; Genin, A.; Genthon, R.; Glasman, P.; Gombert, F.; Habert, M. O.; Hampel, H.; Hewa, H.; Houot, M.; Jungalee, N.; Kas, A.; Kilani, M.; La Corte, V.; Le Roy, F.; Lehericy, S.; Letondor, C.; Levy, M.; Lista, S.; Lowrey, M.; Ly, J.; Makiese, O.; Masetti, I.; Mendes, A.; Metzinger, C.; Michon, A.; Mochel, F.; Nait Arab, R.; Nyasse, F.; Perrin, C.; Poirier, F.; Poisson, C.; Potier, M. C.; Ratovohery, S.; Revillon, M.; Rojkova, K.; Santos-Andrade, K.; Schindler, R.; Servera, M. C.; Seux, L.; Simon, V.; Skovronsky, D.; Thiebaut de Schotten, M.; Uspenskaya, O.; Vlaincu, M.; Aguilar, L. F.; Babiloni, C.; Baldacci, F.; Benda, N.; Black, K. L.; Bokde, A. L. W.; Bonuccelli, U.; Broich, K.; Cacciola, F.; Castrillo, J.; Ceravolo, R.; Colliot, O.; Corvol, J. -C.; Claudio Cuello, A.; Cummings, J. L.; Depypere, H.; Duggento, A.; Durrleman, S.; Escott-Price, V.; Federoff, H.; Teresa Ferretti, M.; Fiandaca, M.; Frank, R. A.; Garaci, F.; Geerts, H.; Genthon, R.; George, N.; Giorgi, F. S.; Graziani, M.; Haberkamp, M.; Herholz, K.; Karran, E.; Kim, S. H.; Koronyo, Y.; Koronyo-Hamaoui, M.; Lamari, F.; Langevin, T.; Lehericy, S.; Lorenceau, J.; Mango, D.; Mapstone, M.; Neri, C.; Nistico, R.; O'Bryant, S. E.; Palermo, G.; Perry, G.; Ritchie, C.; Rossi, S.; Saidi, A.; Santarnecchi, E.; Schneider, L. S.; Sporns, O.; Toschi, N.; Verdooner, S. R.; Villain, N.; Welikovitch, L. A.; Woodcock, J.; Younesi, E.

doi:10.1016/j.jalz.2019.03.006

Introduction:The longitudinal trajectories of functional brain dynamics and the impact of geneticrisk 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 forAlzheimer’s disease, default mode network (DMN) resting state functional connectivity (FC) wasinvestigated between two serial time points across 2 years.Results:Widespread DMN FC changes were shown in frontal and posterior areas, as well as in theright hippocampus. There were no cross-sectional differences, however, apolipoprotein Eε4(APOEε4) carriers demonstrated slower increase in FC in frontal lobes. There was no impact ofindividual brain amyloid load status.Discussion:For the first time, we demonstrated that the pleiotropic biological effect of theAPOEε4allele impacts the dynamic trajectory of the DMN during aging. Dynamic functional biomarkersmay become useful surrogate outcomes for the development of preclinical targeted therapeuticinterventions.