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

Courtney M. Kloske, Michael E. Belloy, Elizabeth E. Blue, Gregory R. Bowman, Maria 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 KhvorovaSascha J. Koppes-den Hertog, Bruce T. Lamb, Paige E. Lawler, Yann Le Guen, Alexandra Litvinchuk, Chia Chen Liu, Simin Mahinrad, Edoardo Marcora, Claudia Marino, Danny M. Michaelson, Justin J. Miller, Josh M. Morganti, Priyanka S. Narayan, Michel S. Naslavsky, Marlies Oosthoek, Kapil V. Ramachandran, Abhirami Ramakrishnan, Ana Caroline Raulin, Aiko Robert, Rasha N.M. Saleh, Claire 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 C. Weninger, Hussein N. Yassine, Na Zhao, Guojun Bu, Alison M. Goate, David M. Holtzman

Research output: Contribution to journalReview articlepeer-review

23 Scopus citations

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.

Original languageEnglish
Pages (from-to)6590-6605
Number of pages16
JournalAlzheimer's and Dementia
Volume20
Issue number9
DOIs
StatePublished - Sep 2024

Bibliographical note

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

Funding

We thank and acknowledge all conference organizers, speakers and session chairs for your tremendous contributions to this conference. M. E. Belloy received funding for this work from the NIH (K99AG075238) and Alzheimer's Association (AARF-20-683984). E. E. Blue was funded by the National Institutes of Health/National Institute on Aging grant number R01AG059737 and is related to her work funded by grant number U01AG058589. G. R. Bowman was funded by NIH grants U19AG069701 and RF1AG067194. X. Chen received the 2023 Early Career Achievement Award from Alzheimer's Association. O. Chiba-Falek was funded in part by the National Institutes of Health/National Institute on Aging (NIH/NIA) [R41 AG077992, R01 AG057522 to OC-F]. A. A. Davis has received research funding that is focused on APOE but which did not directly support this manuscript includes: NIH K08NS101118 DoD W81XWH2010934 NIH RF1AG083753. F. Garretti is funded by F32AG08483. D. Gate is funded by Alzheimer's Association 23AARG-1026607. L. R. Golden is funded by NIH T32 AG078110 “Training in Translational Research in Alzheimer's and Related Dementias (TRIAD)”. J. Heinecke is funded by R01HL149685, R01AG061186. J. Herz acknowledges funding by the NIH, the Brightfocus Foundation and the Alzheimer's Association. Y. Huang is funded by NIH/NIA P01AG073082. C. Iadecola is partially supported by NS126467 ApoE4, neurovascular injury and cognitive impairment. L. A. Johnson is supported by the National Institute on Aging (R01AG060056, R01AG062550, R01AG080589, and R01AG081421), the National Institute of General Medical Sciences (NIGMS) Center of Biomedical Research Excellence in CNS Metabolism P20GM148326, and the Alzheimer's Association. T. Kanekiyo is supported by NIH/NIA U19AG069701. C. M. Karch is funded by NIH-NIA U19 AG069701 Title: Biology and pathobiology of apoE in aging and Alzheimer's Disease. A. Khvorova is funded by GM131839-03. B. T. Lamb is funded by U54 AG065181, U54AG054345, RF1 AG074566. P. E. Lawler is funded by Cure Alzheimer's Fund. Y. Le Guen is supported by the European Union's Horizon 2020 Research and Innovation Program under the Marie Skłodowska-Curie Actions grant 890650 (Dr Le Guen). A. Litvinchuk is funded by BrightFocus Foundation Postdoctoral Fellowship A2022010F (A.L.). E. Marcora is funded by NIH R56AG081417 NIH U19AG069701 BrightFocus Foundation A2017458S. C. Marino is funded by the Edward N. & Della L. Thome Memorial Foundation, from the Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation, from the Remondi Family Foundation, from the US National Institute of Neurological Disorders and Stroke and National Institute on Aging co-funded grants UH3 NS100121 and RF1 NS110048 and from Good Ventures and Open Philanthropy to J.F.A.-V. Grants from the US National Institutes of Health (NIH) Office of the Director grant DP5 OD019833 and US National Institute on Aging grants R01 AG054671, and RF1AG077627, the Massachusetts General Hospital Executive Committee (ECOR) on Research (MGH Research Scholar Award), and grants from the Alzheimer's Association to Y.T.Q. NEI-NIH P30EY003790. D. M. Michaelson received a donation form the Eichenbaum Foundation. J. J. Miller is funded by NIH training grant T32AG05851804. J. M. Morganti is funded by 5R01AG070830, 3RF1NS118558. P. S. Narayan is supported by NIH-NIDDK Intramural Research Program. M. S. Naslavsky is supported by FAPESP13/08028-1 Alzheimer's Association/NIH K24AG053435 CNPq 304746/2022-3. K. V. Ramachandran is supported by NIH Director's Early Independence Award 7DP5OD028133, Department of Defense CDMRP award W81XWH-21-1-0093, Fidelity Biomedical Research Initiative. A. C. Raulin is funded by BrightFocus foundation postdoctoral fellowship A2021015F. R. N. M. Saleh is funded by Medical Research Council (MRC, UK), NuBrain Consortium (MR/T001852/1). F. Shue is supported by U19AG069701. A. Soranno is funded by NIH NIA U19AG069701 (Project 1, A.S.) NIH NIA R01AG062837 (to A.S.). M. R. Strickland has funding provided by the NIH T32 Fellowship (T32AG058518, MRS) and NSF GRFP Fellowship (DGE-1745038, MRS). J. TCW is supported by NIH R01AG082362, R01AG083941, K01AG062683, U19AG069701, R56AG078733. M. Thierry is supported by NIH/NIA grants: P30AG066512 and P01AG060882.R. Tuckey is supported by Alzheimer's Drug Discovery Foundation and NIH grants R01 AG081228, R01 AG068395, and T32 GM008361. J. Ulrich is funded by 1U19AG069701. N. Wang is funded by a NIA U19 grant. C. L. Wellington is supported by Cure Alzheimer Fund and BrightFocus Foundation. H. N. Yassine holds the Kenneth and Bette Volk Endowed Chair of Neurology. HNY is supported by RF1AG076124, RF1AG078362, R01AG067063, R01AG054434, R01AG055770, R21AG056518, and P30AG066530 from the National Institute on Aging, GC-201711-2014197 from the Alzheimer's Drug Discovery Foundation (ADDF), and generous donations from the Vranos and Tiny Foundations and from Ms. Lynne Nauss. N. Zhao is supported by NIH grants U19AG069701, RF1AG046205, R01AG66395, and U54NS110435; a grant from BrightFocus Foundation; and a grant from Cure Alzheimer's Fund. G Bu is supported by Cure Alzheimer's Fund. A. M. Goate receives funding from NIH (U19AG069701, U01AG058635) and the JPB FOundation. D. M. Holtzman is funded by NIH 1U19AG069701 (DMH). We thank and acknowledge all conference organizers, speakers and session chairs for your tremendous contributions to this conference. M. E. Belloy received funding for this work from the NIH (K99AG075238) and Alzheimer's Association (AARF‐20‐683984). E. E. Blue was funded by the National Institutes of Health/National Institute on Aging grant number R01AG059737 and is related to her work funded by grant number U01AG058589. G. R. Bowman was funded by NIH grants U19AG069701 and RF1AG067194. X. Chen received the 2023 Early Career Achievement Award from Alzheimer's Association. O. Chiba‐Falek was funded in part by the National Institutes of Health/National Institute on Aging (NIH/NIA) [R41 AG077992, R01 AG057522 to OC‐F]. A. A. Davis has received research funding that is focused on APOE but which did not directly support this manuscript includes: NIH K08NS101118 DoD W81XWH2010934 NIH RF1AG083753. F. Garretti is funded by F32AG08483. D. Gate is funded by Alzheimer's Association 23AARG‐1026607. L. R. Golden is funded by NIH T32 AG078110 “Training in Translational Research in Alzheimer's and Related Dementias (TRIAD)”. J. Heinecke is funded by R01HL149685, R01AG061186. J. Herz acknowledges funding by the NIH, the Brightfocus Foundation and the Alzheimer's Association. Y. Huang is funded by NIH/NIA P01AG073082. C. Iadecola is partially supported by NS126467 ApoE4, neurovascular injury and cognitive impairment. L. A. Johnson is supported by the National Institute on Aging (R01AG060056, R01AG062550, R01AG080589, and R01AG081421), the National Institute of General Medical Sciences (NIGMS) Center of Biomedical Research Excellence in CNS Metabolism P20GM148326, and the Alzheimer's Association. T. Kanekiyo is supported by NIH/NIA U19AG069701. C. M. Karch is funded by NIH‐NIA U19 AG069701 Title: Biology and pathobiology of apoE in aging and Alzheimer's Disease. A. Khvorova is funded by GM131839‐03. B. T. Lamb is funded by U54 AG065181, U54AG054345, RF1 AG074566. P. E. Lawler is funded by Cure Alzheimer's Fund. Y. Le Guen is supported by the European Union's Horizon 2020 Research and Innovation Program under the Marie Skłodowska‐Curie Actions grant 890650 (Dr Le Guen). A. Litvinchuk is funded by BrightFocus Foundation Postdoctoral Fellowship A2022010F (A.L.). E. Marcora is funded by NIH R56AG081417 NIH U19AG069701 BrightFocus Foundation A2017458S. C. Marino is funded by the Edward N. & Della L. Thome Memorial Foundation, from the Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation, from the Remondi Family Foundation, from the US National Institute of Neurological Disorders and Stroke and National Institute on Aging co‐funded grants UH3 NS100121 and RF1 NS110048 and from Good Ventures and Open Philanthropy to J.F.A.‐V. Grants from the US National Institutes of Health (NIH) Office of the Director grant DP5 OD019833 and US National Institute on Aging grants R01 AG054671, and RF1AG077627, the Massachusetts General Hospital Executive Committee (ECOR) on Research (MGH Research Scholar Award), and grants from the Alzheimer's Association to Y.T.Q. NEI‐NIH P30EY003790. D. M. Michaelson received a donation form the Eichenbaum Foundation. J. J. Miller is funded by NIH training grant T32AG05851804. J. M. Morganti is funded by 5R01AG070830, 3RF1NS118558. P. S. Narayan is supported by NIH‐NIDDK Intramural Research Program. M. S. Naslavsky is supported by FAPESP13/08028‐1 Alzheimer's Association/NIH K24AG053435 CNPq 304746/2022‐3. K. V. Ramachandran is supported by NIH Director's Early Independence Award 7DP5OD028133, Department of Defense CDMRP award W81XWH‐21‐1‐0093, Fidelity Biomedical Research Initiative. A. C. Raulin is funded by BrightFocus foundation postdoctoral fellowship A2021015F. R. N. M. Saleh is funded by Medical Research Council (MRC, UK), NuBrain Consortium (MR/T001852/1). F. Shue is supported by U19AG069701. A. Soranno is funded by NIH NIA U19AG069701 (Project 1, A.S.) NIH NIA R01AG062837 (to A.S.). M. R. Strickland has funding provided by the NIH T32 Fellowship (T32AG058518, MRS) and NSF GRFP Fellowship (DGE‐1745038, MRS). J. TCW is supported by NIH R01AG082362, R01AG083941, K01AG062683, U19AG069701, R56AG078733. M. Thierry is supported by NIH/NIA grants: P30AG066512 and P01AG060882.R. Tuckey is supported by Alzheimer's Drug Discovery Foundation and NIH grants R01 AG081228, R01 AG068395, and T32 GM008361. J. Ulrich is funded by 1U19AG069701. N. Wang is funded by a NIA U19 grant. C. L. Wellington is supported by Cure Alzheimer Fund and BrightFocus Foundation. H. N. Yassine holds the Kenneth and Bette Volk Endowed Chair of Neurology. HNY is supported by RF1AG076124, RF1AG078362, R01AG067063, R01AG054434, R01AG055770, R21AG056518, and P30AG066530 from the National Institute on Aging, GC‐201711‐2014197 from the Alzheimer's Drug Discovery Foundation (ADDF), and generous donations from the Vranos and Tiny Foundations and from Ms. Lynne Nauss. N. Zhao is supported by NIH grants U19AG069701, RF1AG046205, R01AG66395, and U54NS110435; a grant from BrightFocus Foundation; and a grant from Cure Alzheimer's Fund. G Bu is supported by Cure Alzheimer's Fund. A. M. Goate receives funding from NIH (U19AG069701, U01AG058635) and the JPB FOundation. D. M. Holtzman is funded by NIH 1U19AG069701 (DMH).

FundersFunder number
NIH NIDDK
Massachusetts General Hospital Executive Committee
BrightFocus foundation postdoctoral fellowship A2021015F
UK Medical Research Council, Engineering and Physical Sciences Research Council
“Training in Translational Research in Alzheimer's and Related Dementias (TRIAD
National Institutes of Health (NIH)
FAPESP13/08028
Edward N and Della L Thome Memorial Foundation
Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation
JPB Foundation
Fidelity Biomedical Research Initiative
Remondi Family Foundation
NIA/NIHR01AG062837, T32AG058518, U19 AG069701
Horizon 2020
Alzheimer's Drug Discovery FoundationR01 AG081228, T32 GM008361, R01 AG068395, 1U19AG069701
Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke CouncilUH3 NS100121, DP5 OD019833, RF1 NS110048
Alzheimer's AssociationAARF‐20‐683984
Conselho Nacional de Desenvolvimento Científico e Tecnológico7DP5OD028133, 304746/2022‐3
National Institute on AgingT32 AG078110, R01AG061186, R01 AG054671, RF1AG067194, R01 AG057522, RF1AG077627, R41 AG077992, F32AG08483, R01AG059737, U19AG069701, K08NS101118 DoD W81XWH2010934 NIH RF1AG083753, R01HL149685, 23AARG‐1026607, U01AG058589
Cure Alzheimer's FundRF1AG078362, R01AG66395, U01AG058635, R01AG067063, R21AG056518, RF1AG076124, GC‐201711‐2014197, P30AG066530, R01AG055770, RF1AG046205, R01AG054434, U54NS110435
NuBrain ConsortiumMR/T001852/1
ECOR3RF1NS118558, P30EY003790, 5R01AG070830, T32AG05851804
National Science Foundation Arctic Social Science ProgramR01AG082362, P30AG066512, R01AG083941, K01AG062683, R56AG078733, P01AG060882.R, DGE‐1745038
H2020 Marie Skłodowska-Curie Actions890650
U.S. Department of DefenseW81XWH‐21‐1‐0093
BrightFocus FoundationP01AG073082, R01AG062550, R01AG081421, R56AG081417 NIH U19AG069701, A2022010F, NS126467 ApoE4, R01AG080589, R01AG060056
National Institute of General Medical Sciences DP2GM119177 Sophie Dumont National Institute of General Medical SciencesP20GM148326
International Alzheimer's DiseaseU54 AG065181, U54AG054345, GM131839‐03, RF1 AG074566

    Keywords

    • APOE
    • Alzheimer's disease
    • apolipoprotein E
    • conference proceedings
    • dementia
    • lipids
    • microglia
    • neuroinflammation
    • risk factor
    • therapeutics
    • vasculature

    ASJC Scopus subject areas

    • Epidemiology
    • Health Policy
    • Developmental Neuroscience
    • Clinical Neurology
    • Geriatrics and Gerontology
    • Cellular and Molecular Neuroscience
    • Psychiatry and Mental health

    Fingerprint

    Dive into the research topics of 'Advancements in APOE and dementia research: Highlights from the 2023 AAIC Advancements: APOE conference'. Together they form a unique fingerprint.

    Cite this