Advancements in APOE and dementia research: Highlights from the 2023 AAIC Advancements: APOE conference.

Alzheimer's & dementia : the journal of the Alzheimer's Association 2024

Kloske CM, Belloy ME, Blue EE, Bowman GR, Carrillo MC, Chen X, Chiba-Falek O, Davis AA, Paolo GD, Garretti F, Gate D, Golden LR, Heinecke JW, Herz J, Huang Y, Iadecola C, Johnson LA, Kanekiyo T, Karch CM, Khvorova A, Koppes-den Hertog SJ, Lamb BT, Lawler PE, Guen YL, Litvinchuk A, Liu CC, Mahinrad S, Marcora E, Marino C, Michaelson DM

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.

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