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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.

Document Type

Article

Publication Date

9-1-2024

Notes/Citation Information

© 2024 The Author(s). Alzheimer’s & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer’s Association.

Digital Object Identifier (DOI)

https://doi.org/10.1002/alz.13877

Funding Information

NIH, Grant/Award Numbers: K99AG075238, U19AG069701, RF1AG067194, K08NS101118, W81XWH2010934, RF1AG083753, F32AG08483, T32 AG078110, R56AG081417, T32AG05851804, 5R01AG070830, 3RF1NS118558, K24AG053435, 7DP5OD028133, T32AG058518, R01AG082362, R01AG083941, K01AG062683, R56AG078733, R01 AG081228, R01 AG068395, T32 GM008361, 1U19AG069701, RF1AG046205, R01AG66395, U54NS110435, U01AG058635, P30EY003790; Alzheimer’s Association, Grant/Award Numbers: AARF-20-683984, 23AARG-1026607, FAPESP13/08028-1; NIH/NIA, Grant/Award Numbers: R01AG059737, U01AG058589, R41 AG077992, R01 AG057522, P01AG073082, U19AG069701, R01AG062837, P30AG066512, P01AG060882; TRIAD, Grant/Award Numbers: R01HL149685, R01AG061186, P01AG073082; BrightFocus Foundation, Grant/Award Numbers: A2022010F, A2017458S, A2021015F; NS126467 ApoE4, neurovascular injury and cognitive impairment; National Institute on Aging (NIA), Grant/Award Numbers: R01AG060056, R01AG062550, R01AG080589, R01AG081421, R01 AG054671, RF1AG077627, U19, RF1AG076124, RF1AG078362, R01AG067063, R01AG054434, R01AG055770, R21AG056518, P30AG066530; National Institute of General Medical Sciences (NIGMS) Center of Biomedical Research Excellence in CNS Metabolism, Grant/Award Number: P20GM148326; Biology and pathobiology of apoE in aging and Alzheimer’s Disease, Grant/Award Numbers: GM131839-03, U54 AG065181, U54AG054345, RF1 AG074566; Cure Alzheimer’s Fund; Marie Skłodowska-Curie Actions, Grant/Award Number: 890650; Edward N. and Della L. Thome Memorial Foundation; Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation; Remondi Family Foundation; US National Institute of Neurological Disorders and Stroke and National Institute on Aging, Grant/Award Numbers: UH3 NS100121, RF1 NS110048; Good Ventures and Open Philanthropy; NIH Office of the Director, Grant/Award Number: DP5 OD019833; Massachusetts General Hospital Executive Committee (ECOR) on Research; MGH Research Scholar Award; Eichenbaum Foundation; NIH-NIDDK Intramural Research Program; CNPq, Grant/Award Number: 304746/2022-3; Department of Defense, Grant/Award Number: W81XWH-21-1-0093; Fidelity Biomedical Research Initiative; Medical Research Council (MRC, UK); NuBrain Consortium, Grant/Award Number: MR/T001852/1; NSF GRFP Fellowship, Grant/Award Number: DGE-1745038; Alzheimer’s Drug Discovery Foundation, Grant/Award Number: GC-201711-2014197; Cure Alzheimer Fund and BrightFocus Foundation; Kenneth and Bette Volk Endowed Chair of Neurology; Vranos and Tiny Foundations; Ms. Lynne Nauss; JPB Foundation

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