The BDNFVal66Met SNP modulates the association between beta-amyloid and hippocampal disconnection in Alzheimer’s disease
, Nicolai Franzmeier,, Jinyi Ren, , Alexander Damm, , Gemma Monté-Rubio, , Mercè Boada, , Agustín Ruiz, , Alfredo Ramirez, , Frank Jessen, , Emrah Düzel, , Octavio Rodríguez Gómez, , Tammie Benzinger, , Alison Goate, , Celeste M. Karch, , Anne M. Fagan, , Eric McDade, , Katharina Buerger, , Johannes Levin, , Marco Duering, , Martin Dichgans, , Marc Suárez-Calvet, , Christian Haass, , Brian A. Gordon, , Yen Ying Lim, , Colin L. Masters, , Daniel Janowitz, , Cihan Catak, , Steffen Wolfsgruber, , Michael Wagner, , Esther Milz, , Sonia Moreno-Grau, , Stefan Teipel, , Michel J Grothe, , Ingo Kilimann,, Martin Rossor, , Nick Fox, , Christoph Laske, Jasmeer Chhatwal, Peter Falkai, Robert Perneczky, Jae-Hong Lee, Annika Spottke, Henning Boecker, Frederic Brosseron, Klaus Fliessbach, Michael T. Heneka, Peter Nestor, Oliver Peters, Manuel Fuentes, Felix Menne, Josef Priller, Eike J. Spruth, Christiana Franke, Anja Schneider, Christine Westerteicher, Oliver Speck, Jens Wiltfang, Claudia Bartels, Miguel Ángel Araque Caballero, Coraline Metzger, Daniel Bittner, Stephen Salloway, Adrian Danek, Jason Hassenstab, Igor Yakushev, Peter R. Schofield, John C. Morris, Randall J. Bateman & Michael Ewers
This study suggests that BDNFVal66Met is selectively associated with a higher vulnerability of hippocampus-frontal connectivity to primary AD pathology, resulting in greater AD-related cognitive impairment. The effect of BDNFVal66Met on functional networks that may underlie cognitive impairment in AD is poorly understood. Using a cross-validation approach, we first explored in subjects with autosomal dominant AD (ADAD) from the Dominantly Inherited Alzheimer Network (DIAN) the effect of BDNFVal66Met on resting-state fMRI assessed functional networks.