Advancements in APOE and dementia research: Highlights from the 2023 AAIC Advancements: APOE conference
Courtney M. Kloske, Michaël E. Belloy, Elizabeth Blue, Gregory R. Bowman, María C. Carrillo, Xiaoying Chen, Ornit Chiba‐Falek, Albert A. Davis, Gilbert Di Paolo, Francesca Garretti, David Gate, Lesley R. Golden, Jay W. Heinecke, Joachim Herz, Yadong Huang, Costantino Iadecola, Lance A. Johnson, Takahisa Kanekiyo, Celeste M. Karch, Anastasia Khvorova, Sascha J. Koppes‐den Hertog, Bruce T. Lamb, Paige E. Lawler, Yann Le Guen, Alexandra Litvinchuk, Chia‐Chen Liu, Simin Mahinrad, Edoardo Marcora, Claudia Mariño, D. M. Michaelson, Justin J. Miller, Josh M. Morganti, Priyanka Narayan, Michel Satya Naslavsky, Marlies Oosthoek, Kapil V. Ramachandran, Abhirami Ramakrishnan, Ana‐Caroline Raulin, Aiko Robert, Rasha N.M. Saleh, Claire E. Sexton, Nilomi Shah, Francis Shue, Isabel J. Sible, Andrea Soranno, Michael R. Strickland, Julia TCW, Manon Thierry, Li‐Huei Tsai, Ryan A. Tuckey, Jason D. Ulrich, Rik van der Kant, Na Wang, Cheryl L. Wellington, Stacie Weninger, Hussein N. Yassine, Na Zhao, Guojun Bu, Alison Goate, David M. Holtzman
Abstract
INTRODUCTION: The apolipoprotein E gene (APOE) is an established central player in the pathogenesis of Alzheimer's disease (AD), with distinct apoE isoforms exerting diverse effects. apoE influences not only amyloid-beta and tau pathologies but also lipid and energy metabolism, neuroinflammation, cerebral vascular health, and sex-dependent disease manifestations. Furthermore, ancestral background may significantly impact the link between APOE and AD, underscoring the need for more inclusive research. METHODS: In 2023, the Alzheimer's Association convened multidisciplinary researchers at the "AAIC Advancements: APOE" conference to discuss various topics, including apoE isoforms and their roles in AD pathogenesis, progress in apoE-targeted therapeutic strategies, updates on disease models and interventions that modulate apoE expression and function. RESULTS: This manuscript presents highlights from the conference and provides an overview of opportunities for further research in the field. DISCUSSION: Understanding apoE's multifaceted roles in AD pathogenesis will help develop targeted interventions for AD and advance the field of AD precision medicine. HIGHLIGHTS: APOE is a central player in the pathogenesis of Alzheimer's disease. APOE exerts a numerous effects throughout the brain on amyloid-beta, tau, and other pathways. The AAIC Advancements: APOE conference encouraged discussions and collaborations on understanding the role of APOE.