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

Department of Neurobiology

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

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
Journal	Alzheimer's and Dementia
DOIs	https://doi.org/10.1002/alz.13877
State	Accepted/In press - 2024

Funding

Funders	Funder number
Massachusetts General Hospital Executive Committee
BrightFocus foundation postdoctoral fellowship A2021015F
Medical Research Council
“Training in Translational Research in Alzheimer's and Related Dementias (TRIAD
Edward N. and Della L. Thome Memorial Foundation
Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation
JPB Foundation
European Union's Horizon 2020 research and innovation program
NIH‐NIDDK
Remondi Family Foundation
Alzheimer's Drug Discovery Foundation	R01 AG081228, T32 GM008361, R01 AG068395, 1U19AG069701
Alzheimer's Drug Discovery Foundation
NIA	R41 AG077992, F32AG08483, R01AG061186, T32 AG078110, R01HL149685, 23AARG‐1026607, R01 AG057522
NIH NIA	R01AG062837, T32AG058518
Cure Alzheimer's Fund	RF1AG078362, R01AG66395, U01AG058635, R21AG056518, R01AG067063, RF1AG076124, GC‐201711‐2014197, P30AG066530, R01AG055770, RF1AG046205, R01AG054434, U54NS110435
Cure Alzheimer's Fund
NIH‐NIA	U19 AG069701
U.S. Department of Defense	W81XWH‐21‐1‐0093
U.S. Department of Defense
National Institute of Neurological Disorders and Stroke	UH3 NS100121, RF1 NS110048
National Institute of Neurological Disorders and Stroke
Alzheimer's Association	AARF‐20‐683984
Alzheimer's Association
BrightFocus Foundation	P01AG073082, R01AG062550, R56AG081417 NIH U19AG069701, R01AG081421, A2022010F, NS126467 ApoE4, R01AG080589, R01AG060056
BrightFocus Foundation
National Institute on Aging	RF1AG077627, R01 AG054671, R01AG059737, U19AG069701, U01AG058589, RF1AG067194
National Institute on Aging
NuBrain Consortium	MR/T001852/1
Alzheimer's Disease	U54 AG065181, U54AG054345, GM131839‐03, RF1 AG074566
National Institutes of Health	DP5 OD019833
National Institutes of Health
National Institute of General Medical Sciences	P20GM148326
National Institute of General Medical Sciences
ECOR	3RF1NS118558, P30EY003790, 5R01AG070830, T32AG05851804
CNPq	7DP5OD028133, 304746/2022‐3
NSF	R01AG082362, P30AG066512, R01AG083941, K01AG062683, R56AG078733, P01AG060882.R, DGE‐1745038
H2020 Marie Skłodowska-Curie Actions	890650
H2020 Marie Skłodowska-Curie Actions

Keywords

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

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10.1002/alz.13877

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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. (Accepted/In press). Advancements in APOE and dementia research: Highlights from the 2023 AAIC Advancements: APOE conference. Alzheimer's and Dementia. https://doi.org/10.1002/alz.13877

@article{064a2f8240474589bc4b1020aa5090c4,

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",

doi = "10.1002/alz.13877",

language = "אנגלית",

journal = "Alzheimer's and Dementia",

issn = "1552-5260",

publisher = "Elsevier Inc.",

}

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. 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

Y1 - 2024

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

U2 - 10.1002/alz.13877

DO - 10.1002/alz.13877

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.systematicreview???

C2 - 39031528

AN - SCOPUS:85199158570

SN - 1552-5260

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

ER -

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

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