Accès ouvert déclaré
2026
article
Genetic modifiers of APOE-ε4-associated cognitive decline
Alex G. Contreras, Skylar Walters, Jaclyn M. Eissman, Derek B. Archer, Alexandra N. Regelson, Alaina Durant, Michelle Clifton, Shubhabrata Mukherjee, Michael L. Lee, Seo-eun Choi, Phoebe Scollard, Emily H. Trittschuh, Jesse Mez, William S. Bush, Brian W. Kunkle, Carlos Cruchaga, Adam C. Naj, Katherine A. Gifford, Murat Bilgel, Amanda B. Kuzma, The Alzheimer’s Disease Neuroimaging Initiative (ADNI), Michael Weiner, Paul Aisen, Ronald C. Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, John C. Morris, Leslie M. Shaw, Enchi Liu, Tom Montine, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Danielle Harvey, Matthew Bernstein, Nick Fox, Norbert Schuff, Charles DeCarli, Bret Borowski, Jeff Gunter, Matt Senjem, Prashanthi Vemuri, David B. Jones, Kejal Kantarci, Chad Ward, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Chet Mathis, Susan Landau, Nigel J. Cairns, Erin Householder, Lisa Taylor Reinwald, Virginia Lee, Magdalena Korecka, Michal Figurski, Karen Crawford, Scott Neu, Tatiana M. Foroud, Steven Potkin, Li Shen, Faber Kelley, Sungeun Kim, Kwangsik Nho, Zaven Kachaturian, Richard Frank, Peter J. Snyder, Molchan Se, Jeffrey A. Kaye, Joseph Quinn, Betty Ann Lind, Raina Carter, Sara Dolen, Lon S. Schneider, Sonia Pawluczyk, Mauricio Beccera, Liberty Teodoro, Bryan M. Spann, James B. Brewer, Helen Vanderswag, Adam Fleisher, Judith L. Heidebrink, Joanne L. Lord, Sara S. Mason, Colleen S. Albers, David Knopman, Kris Johnson, Rachelle S. Doody, Javier Villanueva Meyer, Munir Chowdhury, Susan Rountree, Mimi Dang, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, Beau Ances, Maria Carroll, Sue Leon, Mark A. Mintun, Stacy R. Schneider, Angela Oliver, Daniel C. Marson, Randall Griffith, David Clark, David Geldmacher, John Brockington, Erik D. Roberson, Hillel Grossman, Effie Mitsis, Leyla deToledo-Morrell, Raj C. Shah, Ranjan Duara, Daniel Varon, Maria T. Greig, Peggy Roberts, Chiadi Onyike, Daniel D’Agostino, Stephanie Kielb, James E. Galvin, Dana M. Pogorelec, Brittany Cerbone, Christina A. Michel, Henry Rusinek, Mony J. de Leon, Lidia Glodzik, Susan M De Santi, P. Murali Doraiswamy, Jeffrey R. Petrella, Terence Wong, Steven E. Arnold, Jason H. Karlawish, David Wolk, Charles D. Smith, Greg Jicha, Peter Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad, Oscar L. Lopez, MaryAnn Oakley, Donna M. Simpson, Anton P. Porsteinsson, Bonnie S. Goldstein, Kim Martin, Kelly M. Makino, M. Saleem Ismail, Connie Brand, Ruth A. Mulnard, Gaby Thai, Catherine Mc Adams Ortiz, Kyle Womack, Dana Mathews, Mary Quiceno, Ramon Diaz Arrastia, Richard King, Myron Weiner, Michael DeVous, Allan I. Levey, James J. Lah, Janet S. Cellar, Jeffrey M. Burns, Heather S. Anderson, Russell H. Swerdlow, Liana Apostolova, Kathleen Tingus, Ellen Woo, Daniel. H. S. Silverman, Po H. Lu, George Bartzokis, Neill R. Graff Radford, Francine Parfitt, Tracy Kendall, H. R. M. Johnson, Martin R. Farlow, Ann Marie Hake, Brandy R. Matthews, Scott Herring, Cynthia Hunt, Christopher H. van Dyck, Richard E. Carson, Martha G. MacAvoy, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra Black, Bojana Stefanovic, Curtis B. Caldwell, Ging Yuek Robin Hsiung, Benita Mudge, Michele Assaly, Andrew Kertesz, John Rogers, Charles Bernick, Diana Kerwin, Marek Marsel Mesulam, Kristine Lipowski, Chuang Kuo Wu, Nancy Johnson, Carl Sadowsky, Walter Martinez, Teresa Villena, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Keith A. Johnson, Gad Marshall, Meghan Frey, Jerome Yesavage, Joy L. Taylor, Barton Lane, A ROSEN, Jared Tinklenberg, Marwan N. Sabbagh, Christine M. Belden, Sandra Jacobson, Sherye A. Sirrel, Neil W. Kowall, Ronald Killiany, Andrew E. Budson, Alexander Norbash, Patricia Lynn Johnson, Thomas O. Obisesan, Saba Wolday, Joanne L. Allard, Alan J. Lerner, Paula Ogrocki, Leon Hudson, Evan Fletcher, Owen Carmichael, Smita Kittur, Michael Borrie, T. Y. Lee, Dr Rob Bartha, Sanjay Asthana, Cynthia M. Carlsson, Adrian Preda, Dana Nguyen, Pierre Tariot, Stephanie Reeder, Vernice Bates, Horacio Capote, Michelle Rainka, Douglas W. Scharre, Maria Kataki, Anahita Adeli, Earl A. Zimmerman, Dzintra Celmins, Alice D. Brown, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Robert B. Santulli, Tamar J. Kitzmiller, E. Schwartz, Kaycee M. Sink, Jeff D. Williamson, Pradeep Garg, Franklin Watkins, Brian R. Ott, Henry Querfurth, Geoffrey Tremont, Stephen Salloway, Paul Malloy, Stephen Correia, Howard J. Rosen, Bruce L. Miller, Jacobo Mintzer, Kenneth Spicer, David Bachman, Elizabether Finger, Stephen Pasternak, Irina Rachinsky, Dick J. Drost, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Susan K. Schultz, Laura L. Boles Ponto, HyungSub Shim, Karen Elizabeth Smith, Norman Relkin, Gloria Chaing, Lisa Raudin, Amanda Smith, Kristin Fargher, Balebail Ashok Raj, Eveleen Darby, Paul J. Massman, Valory Pavlik, Monica Rodriguear, Matthew P. Frosch, Hakon Hakonarson, Thomas Wisniewski, John M. Olichney, Marcia Ory, Alan Stevens, Thomas G. Beach, Jagan A. Pillai, James B. Leverenz, Tamar Gefen, Robert Vassar, John S. K. Kauwe, Gyungah R Jun, Kathryn L. Lunetta, Katrina Bazemore, Taha Iqbal, Jin Sha, Bárbara Davis, Linda S. Hynan, Bruce Jones, Joan Reisch, Jackie Bartlett, Penelope Benchek, Yeunjoo E. Song, Nick Wheeler, Victor Henderson, Deborah Blacker, Sarah Biber, Kwun C. Chan, Yen‐Chi Chen, Jessica E. Culhane, Nic Dobbins, Kathryn Gauthreaux, B Keller, Melissa Lerch, Charles Mock, Sean D. Mooney, Kyle Ormsby, Raymond Palmer, Marsha Polk, Jeffrey Tilson, Kirk C. Wilhelmsen, Gail P. Jarvik, Ellen Wijsman, Douglas B. Mains, M. Ilyas Kamboh, Joseph E. Parisi, Kelley M. Faber, Kathleen Hall, Donghe Li, Xiaoling Zhang, John Farrell, Xudong Han, Moon Il Kang, Logue Mark, Richard M. Sherva, Congcong Zhu, James R. Burke, Kathleen A. Welsh-Bohmer, Eric B. Larson, W. C. McCormick, Craig Atwood, Mark A. Sager, Frank M. LaFerla, David Marquez, Lei Yu, Mindy J. Katz, Richard B. Lipton, Ann C. McKee, Robert A. Stern, Thomas S. Wingo, Bradley T. Hyman, John H. Growdon, Bradley F. Boeve, Vijay Ramanan, Deborah C. Mash, Oscar Harari, Joseph F. Quinn, Harry V. Vinters, Adam Boxer, William W. Seeley, Roger L. Albin, Helena C. Chui, John M. Ringman, Alyssa Aguirre, David Paydarfar, Roger N. Rosenberg, Thomas D. Bird, Thomas Grabowski, Suman Jayadev, Joel H. Kramer, Mariet Allen, Minerva M. Carrasquillo, Dennis W. Dickson, Nilufer Ertekin-Taner, Neill R. Graff-Radford, Steven G. Younkin, Joseph D. Buxbaum, Alison M. Goate, Brian Fulton-Howard, Douglas R. Galasko, Ronald L. Hamilton, Bernardino Ghetti, Lee-Way Jin, Elizabeth Head, Ronald Kim, Edwin S. Monuki, Vivianna M. Van Deerlin, Xiongwei Zhu, Juan C. Troncoso, Marsel Mesulam, Sandra Weintraub, Randall L. Woltjer, Thomas J. Montine, Kenneth B. Fallon, Andrew P. Lieberman, Robert C. Barber, James W Hall III, Leigh Johnson, Grunin Michelle, Ellen L. Palmer, David L. Sultzer, Amanda Myers, Elizabeth A. Crocco, Laura Ibanez, Constantine G. Lyketsos, Abhay Moghekar, Mary Sano, Arjun V. Masurkar, John Bertelson, Munro C. Cullum, Daniele Fallin, Kelley Nudelman, Ryan M. Huebinger, John C. DeToledo, Michelle Hernandez, Kimberly Johnson, Victoria Perez, Henrick Wilms, Donald R. Royall, James T. Becker, Clinton B. Wright, Nathaniel A. Chin, Suzanne Craft, Howard Andrews, John Hardy, Janice Knebl, Sid E. O’Bryant, Regina M. Carney, Henry L. Paulson, Duane Beekly, Marie-Françoise Chesselet, Daniel H. Geschwind, Matthew J. Huentelman, Beth A. Dombroski, Pavel P. Kuksa, Wan-Ping Lee, Laura B. Cantwell, Marissa Cranney, Yuk Yee Leung, Liming Qu, Otto Valladares, Yi Zhao, Stephen Strittmatter, Philip L. De Jager, Jeffrey L. Tilson, Denis A. Evans, Erin L. Abner, Linda J. Van Eldik, David W. Fardo, Susan M. McCurry, Goldie Byrd, Ekaterina Rogaeva, George-Hyslop Peter St., Jean-Paul Vonsattel, Sandra Barral, Jennifer Manly, James M. Noble, Christiane Reitz, Andrew Teich, Giuseppe Tosto, Badri N. Vardarajan, Jennifer Williamson, Gary W. Beecham, John R. Gilbert, Anthony R. Griswold, Farid Rajabli, Jeffery M. Vance, Susan H. Slifer, Patrice L. Whitehead, Chuanhai Cao, Debby W. Tsuang, The Alzheimer's Disease Sequencing Project (ADSP), Eric Boerwinkle, Richard Gibbs, Kim Worley, Nancy Heard-Costa, Moon-Il Kang, Zainab Kurshid, Tong Tong, Benjamin Wolozin, Marlene Tejeda, Xinyu Sun, Jaeyoon Chung, Kathy Lunetta, Anita DeStefano, Gina Peloso, Achilleas Pitsillides, Keoni Kauwe, Audrey Lynn, Scott Williams, Nicolas J. Wheeler, Jungsoo Gim, Sandra Barral Rodriguez, Phil L. de Jager, Suzanne Leal, Yiyi Ma, Richard Mayeux, Dolly Reyes-Dumeyer, Shahzhad Ahmad, Hata Čomić, Hannah Craft, Taeho Jo, Shannon Risacher, Min Soo Byun, Dong Young Lee, Dahyun Yi, John McNeil, Shea J Andrews, Jack Humphrey, Dado Marcora, Tulsi Patel, Towfique Raj, Alan Renton, Andrew Sharp, Ricardo Vialle, Kelly Nudelman, K Lacy, David G. Knowles, Chirag M. Lakhani, Anjali Das, Teresa Lin, Yun Freudenberg‐Hua, Sungho Wang, Michael Greicius, Anshul Kundaje, Stephen Montgomery, Ryan Corces, Vilmundur Guðnason, Kara Hamilton-Nelson, Nicholas A. Kushch, Pedro R Mena, Mike Schmidt, Karen Nuytemans, Larry D. Adams, Sharon Kardia, Jennifer Smith, Wei Zhao, Najaf Amin, Cornelia van Duijn, Yi‐Fan Chou, Christos Davatzikos, Heather Nicaretta, F. Leung, John Malamon, Alexis Lerro Rose, Andy Wilk, Beth Dombrosk, Emily Greenfest‐Allen, Flawless Robbins, Heather White, Jacob Haut, Jascha Brettschneider, Jeffrey Cifello, Joseph Manuel, Lauren Bass, Luke Carter, Maureen Kirsch, Michelle K Moon, Naveensri Saravanan, Pei‐Chuan Ho, Peter Keskinen, Prabhakaran Gangadharan, Sam Tate, Wei‐Hsuan Chuang, Wen-Hwai Horng, Youli Ren, Yumi Jin, Živadin Katanić, Robert Babak Frayabi, Ming Li, Kamnaa Arya, Heng Huang, Sophia I Thomopolous, Myriam Fornage, Chloé Sarnowski, Josh Bis, Liz Blue, Andrea Horimoto, Rafael A. Nafikov, Tim Thornton, Seth D Temple, Tyler Day, Eugine Lin, Bruce Psaty, Dagmar Bačíková, Clifton Dalgard, Bernard Fongang, Xueqiu Jian, Muralidharan Sargurupremraj, Claudia Satizabal, Sudha Seshadri, Habil Zare, Jose Bras, Rita Guerreiro, Piper Below, Susan Dutcher, Victoria Fernandez, Achal Neupane, Jung Ying Tzeng, Shin‐Yi Chou, Alessandra F. A. Chesi, Struan F. A. Grant, Michael L. Cuccaro, Margaret A. Pericak-Vance, Lindsay A. Farrer, Li-San Wang, Gerard D. Schellenberg, Jonathan L. Haines, Angela L. Jefferson, Walter A. Kukull, C. Dirk Keene, Andrew J. Saykin, Paul M. Thompson, Eden R. Martin, Marilyn S. Albert, Sterling C. Johnson, Corinne D. Engelman, Luigi Ferrucci, David A. Bennett, Lisa Laverne Barnes, Julie A. Schneider, Reisa A. Sperling, Susan M. Resnick, Paul K. Crane, Logan Dumitrescu, Timothy J. Hohman
3Citations signalées — pas une note de qualité
124Institutions déclarées
7Pays d’affiliation déclarés
Résumé fourni par la source
The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer's disease. However, APOE-ε4 is not deterministic, highlighting the need to identify additional genetic and environmental factors. APOE-ε4 has been linked to accelerated cognitive decline, so we sought to investigate genetic factors that modify APOE-ε4-associated cognitive decline. We conduct cross-ancestry APOE-ε4-stratified and interaction GWAS using harmonized cognitive data from 32,778 participants, including 29,354 non-Hispanic White and 3,424 non-Hispanic Black individuals. Our primary outcome is late-life cognition, measured using harmonized composite scores for memory, executive function, and language, modeled as continuous traits reflecting both normative cognitive aging and disease-related decline. We identify two genome-wide significant loci in APOE-ε4 carriers, reaching genome-wide significance for executive function. These loci also demonstrate nominal associations across the other domains, suggesting broad effects on cognition. In non-carriers, we identify a genome-wide significant association at ITGB8 restricted to executive function, and another locus associated with language. We further link these loci to SEMA6D, GRIN3A, and ITGB8 through expression and methylation databases. Post-GWAS analyses implicate additional genes including SLCO1A2, and DNAH11. Genetic correlation analyses reveal differences by APOE-ε4 status for immune-related traits, suggesting immune-related predispositions may exacerbate cognitive risk in APOE-ε4 carriers.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Genetic modifiers of APOE-ε4-associated cognitive decline
- Date Crossref
- 20/02/2026
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude et ne compte pas comme une seconde source scientifique indépendante.
Institutions déclarées
Une affiliation ne permet pas de déduire la nationalité d’un auteur.
Sujets associés
Dementia and Cognitive Impairment ResearchGenetic Associations and EpidemiologyAlzheimer's disease research and treatments