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 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 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

doi:10.1002/alz.13877

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

^*Corresponding author for this work

Neurology

Research output: Contribution to journal › Review article › peer-review

6 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 language	English (US)
Pages (from-to)	6590-6605
Number of pages	16
Journal	Alzheimer's and Dementia
Volume	20
Issue number	9
DOIs	https://doi.org/10.1002/alz.13877
State	Published - Sep 2024

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 \u201CTraining in Translational Research in Alzheimer's and Related Dementias (TRIAD)\u201D. 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 Sk\u0142odowska-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\u201020\u2010683984). 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\u2010Falek was funded in part by the National Institutes of Health/National Institute on Aging (NIH/NIA) [R41 AG077992, R01 AG057522 to OC\u2010F]. 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\u20101026607. L. R. Golden is funded by NIH T32 AG078110 \u201CTraining in Translational Research in Alzheimer's and Related Dementias (TRIAD)\u201D. 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\u2010NIA U19 AG069701 Title: Biology and pathobiology of apoE in aging and Alzheimer's Disease. A. Khvorova is funded by GM131839\u201003. 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 Sk\u0142odowska\u2010Curie 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\u2010funded grants UH3 NS100121 and RF1 NS110048 and from Good Ventures and Open Philanthropy to J.F.A.\u2010V. 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\u2010NIH 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\u2010NIDDK Intramural Research Program. M. S. Naslavsky is supported by FAPESP13/08028\u20101 Alzheimer's Association/NIH K24AG053435 CNPq 304746/2022\u20103. K. V. Ramachandran is supported by NIH Director's Early Independence Award 7DP5OD028133, Department of Defense CDMRP award W81XWH\u201021\u20101\u20100093, 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\u20101745038, 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\u2010201711\u20102014197 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).

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1002/alz.13877

Cite this

Kloske, C. M., Belloy, M. E., Blue, E. E., Bowman, G. R., Carrillo, M. C., Chen, X., Chiba-Falek, O., Davis, A. A., Paolo, G. D., Garretti, F., Gate, D., Golden, L. R., Heinecke, J. W., Herz, J., Huang, Y., Iadecola, C., Johnson, L. A., Kanekiyo, T., Karch, C. M., ... Holtzman, D. M. (2024). Advancements in APOE and dementia research: Highlights from the 2023 AAIC Advancements: APOE conference. Alzheimer's and Dementia, 20(9), 6590-6605. https://doi.org/10.1002/alz.13877

@article{cb948e622e6b418f8dd4d5774ebc9845,

title = "Advancements in APOE and dementia research: Highlights from the 2023 AAIC Advancements: APOE conference",

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.",

keywords = "APOE, Alzheimer's disease, apolipoprotein E, conference proceedings, dementia, lipids, microglia, neuroinflammation, risk factor, therapeutics, vasculature",

author = "Kloske, {Courtney M.} and Belloy, {Michael E.} and Blue, {Elizabeth E.} and Bowman, {Gregory R.} and Carrillo, {Maria C.} and Xiaoying Chen and Ornit Chiba-Falek and Davis, {Albert A.} and Paolo, {Gilbert Di} and Francesca Garretti and David Gate and Golden, {Lesley R.} and Heinecke, {Jay W.} and Joachim Herz and Yadong Huang and Costantino Iadecola and Johnson, {Lance A.} and Takahisa Kanekiyo and Karch, {Celeste M.} and Anastasia Khvorova and {Koppes-den Hertog}, {Sascha J.} and Lamb, {Bruce T.} and Lawler, {Paige E.} and Guen, {Yann Le} and Alexandra Litvinchuk and Liu, {Chia Chen} and Simin Mahinrad and Edoardo Marcora and Claudia Marino and Michaelson, {Danny M.} and Miller, {Justin J.} and Morganti, {Josh M.} and Narayan, {Priyanka S.} and Naslavsky, {Michel S.} and Marlies Oosthoek and Ramachandran, {Kapil V.} and Abhirami Ramakrishnan and Raulin, {Ana Caroline} and Aiko Robert and Saleh, {Rasha N.M.} and Claire Sexton and Nilomi Shah and Francis Shue and Sible, {Isabel J.} and Andrea Soranno and Strickland, {Michael R.} and Julia Tcw and Manon Thierry and Tsai, {Li Huei} and Tuckey, {Ryan A.} and Ulrich, {Jason D.} and {van der Kant}, Rik and Na Wang and Wellington, {Cheryl L.} and Weninger, {Stacie C.} and Yassine, {Hussein N.} and Na Zhao and Guojun Bu and Goate, {Alison M.} and Holtzman, {David M.}",

note = "Publisher Copyright: {\textcopyright} 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.",

year = "2024",

month = sep,

doi = "10.1002/alz.13877",

language = "English (US)",

volume = "20",

pages = "6590--6605",

journal = "Alzheimer's and Dementia",

issn = "1552-5260",

publisher = "John Wiley and Sons Inc.",

number = "9",

}

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, Miller, JJ, Morganti, JM, Narayan, PS, Naslavsky, MS, Oosthoek, M, Ramachandran, KV, Ramakrishnan, A, Raulin, AC, Robert, A, Saleh, RNM, Sexton, C, Shah, N, Shue, F, Sible, IJ, Soranno, A, Strickland, MR, Tcw, J, Thierry, M, Tsai, LH, Tuckey, RA, Ulrich, JD, van der Kant, R, Wang, N, Wellington, CL, Weninger, SC, Yassine, HN, Zhao, N, Bu, G, Goate, AM & Holtzman, DM 2024, 'Advancements in APOE and dementia research: Highlights from the 2023 AAIC Advancements: APOE conference', Alzheimer's and Dementia, vol. 20, no. 9, pp. 6590-6605. https://doi.org/10.1002/alz.13877

TY - JOUR

T1 - Advancements in APOE and dementia research

T2 - Highlights from the 2023 AAIC Advancements: APOE conference

AU - Kloske, Courtney M.

AU - Belloy, Michael E.

AU - Blue, Elizabeth E.

AU - Bowman, Gregory R.

AU - Carrillo, Maria C.

AU - Chen, Xiaoying

AU - Chiba-Falek, Ornit

AU - Davis, Albert A.

AU - Paolo, Gilbert Di

AU - Garretti, Francesca

AU - Gate, David

AU - Golden, Lesley R.

AU - Heinecke, Jay W.

AU - Herz, Joachim

AU - Huang, Yadong

AU - Iadecola, Costantino

AU - Johnson, Lance A.

AU - Kanekiyo, Takahisa

AU - Karch, Celeste M.

AU - Khvorova, Anastasia

AU - Koppes-den Hertog, Sascha J.

AU - Lamb, Bruce T.

AU - Lawler, Paige E.

AU - Guen, Yann Le

AU - Litvinchuk, Alexandra

AU - Liu, Chia Chen

AU - Mahinrad, Simin

AU - Marcora, Edoardo

AU - Marino, Claudia

AU - Michaelson, Danny M.

AU - Miller, Justin J.

AU - Morganti, Josh M.

AU - Narayan, Priyanka S.

AU - Naslavsky, Michel S.

AU - Oosthoek, Marlies

AU - Ramachandran, Kapil V.

AU - Ramakrishnan, Abhirami

AU - Raulin, Ana Caroline

AU - Robert, Aiko

AU - Saleh, Rasha N.M.

AU - Sexton, Claire

AU - Shah, Nilomi

AU - Shue, Francis

AU - Sible, Isabel J.

AU - Soranno, Andrea

AU - Strickland, Michael R.

AU - Tcw, Julia

AU - Thierry, Manon

AU - Tsai, Li Huei

AU - Tuckey, Ryan A.

AU - Ulrich, Jason D.

AU - van der Kant, Rik

AU - Wang, Na

AU - Wellington, Cheryl L.

AU - Weninger, Stacie C.

AU - Yassine, Hussein N.

AU - Zhao, Na

AU - Bu, Guojun

AU - Goate, Alison M.

AU - Holtzman, David M.

PY - 2024/9

Y1 - 2024/9

N2 - 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.

AB - 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.

KW - APOE

KW - Alzheimer's disease

KW - apolipoprotein E

KW - conference proceedings

KW - dementia

KW - lipids

KW - microglia

KW - neuroinflammation

KW - risk factor

KW - therapeutics

KW - vasculature

UR - http://www.scopus.com/inward/record.url?scp=85199158570&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85199158570&partnerID=8YFLogxK

U2 - 10.1002/alz.13877

DO - 10.1002/alz.13877

M3 - Review article

C2 - 39031528

AN - SCOPUS:85199158570

SN - 1552-5260

VL - 20

SP - 6590

EP - 6605

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 9

ER -

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

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this