Patrizia A Chiesa1, Enrica Cavedo2, Andrea Vergallo2, Simone Lista2, Marie-Claude Potier3, Marie-Odile Habert4, Bruno Dubois2, Michel Thiebaut de Schotten5, Harald Hampel6. 1. Sorbonne University, GRC no 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Boulevard de l'hôpital, Paris, France; Brain & Spine Institute (ICM), INSERM U 1127, CNRS UMR 7225, Boulevard de l'hôpital, Paris, France; Department of Neurology, Institute of Memory and Alzheimer's Disease (IM2A), Pitié-Salpêtrière Hospital, AP-HP, Boulevard de l'hôpital, Paris, France. Electronic address: po.chiesa@gmail.com. 2. Sorbonne University, GRC no 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Boulevard de l'hôpital, Paris, France; Brain & Spine Institute (ICM), INSERM U 1127, CNRS UMR 7225, Boulevard de l'hôpital, Paris, France; Department of Neurology, Institute of Memory and Alzheimer's Disease (IM2A), Pitié-Salpêtrière Hospital, AP-HP, Boulevard de l'hôpital, Paris, France. 3. ICM Institut du Cerveau et de la Moelleépinière, CNRS UMR7225, INSERM U1127, UPMC, Hôpital de la Pitié-Salpêtrière, 47 Bd de l'Hôpital, Paris, France. 4. Laboratoire d'Imagerie Biomédicale, Sorbonne Université, INSERM U 1146, CNRS UMR, Paris, France; Department of Nuclear Medicine, AP-HP, HôpitalPitié-Salpêtrière, Paris, France; Centre Acquisition et Traitement des Images (CATI), Paris, France. 5. Brain & Spine Institute (ICM), INSERM U 1127, CNRS UMR 7225, Boulevard de l'hôpital, Paris, France; Laboratory of Alzheimer's Neuroimaging and Epidemiology, IRCCS Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy; Brain Connectivity Behaviour Laboratory, Sorbonne Universities, Paris, France; Groupe d'Imagerie Neurofonctionnelle, Institut des Maladies Neurodégénératives-UMR 5293, CNRS, CEA University of Bordeaux, Bordeaux, France. 6. Sorbonne University, GRC no 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Boulevard de l'hôpital, Paris, France.
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 functional connectivity (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 E ε4 (APOE ε4) 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 pleiotropic biological effect of the APOE ε4 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.
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 functional connectivity (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 E ε4 (APOE ε4) 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 pleiotropic biological effect of the APOE ε4 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.
Authors: Omar H Butt; Karin L Meeker; Julie K Wisch; Suzanne E Schindler; Anne M Fagan; Tammie L S Benzinger; Carlos Cruchaga; David M Holtzman; John C Morris; Beau M Ances Journal: Alzheimers Dement Date: 2021-05-18 Impact factor: 21.566
Authors: Harald Hampel; Robert Vassar; Bart De Strooper; John Hardy; Michael Willem; Neeraj Singh; John Zhou; Riqiang Yan; Eugeen Vanmechelen; Ann De Vos; Robert Nisticò; Massimo Corbo; Bruno Pietro Imbimbo; Johannes Streffer; Iryna Voytyuk; Maarten Timmers; Amir Abbas Tahami Monfared; Michael Irizarry; Bruce Albala; Akihiko Koyama; Naoto Watanabe; Teiji Kimura; Lisa Yarenis; Simone Lista; Lynn Kramer; Andrea Vergallo Journal: Biol Psychiatry Date: 2020-02-13 Impact factor: 13.382
Authors: Filippo Baldacci; Simone Lista; Maria Laura Manca; Patrizia A Chiesa; Enrica Cavedo; Pablo Lemercier; Henrik Zetterberg; Kaj Blennow; Marie-Odile Habert; Marie Claude Potier; Bruno Dubois; Andrea Vergallo; Harald Hampel Journal: Alzheimers Res Ther Date: 2020-11-12 Impact factor: 8.823
Authors: Indira C Turney; Anthony G Chesebro; Miguel Arce Rentería; Patrick J Lao; Juliet M Beato; Nicole Schupf; Richard Mayeux; Jennifer J Manly; Adam M Brickman Journal: Alzheimers Dement (Amst) Date: 2020-09-22