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APOE Christchurch-mimetic therapeutic antibody reduces APOE-mediated toxicity and tau phosphorylation

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APOE Christchurch-mimetic therapeutic antibody reduces APOE-mediated toxicity and tau phosphorylation. / Marino, Claudia; Perez-Corredor, Paula; O'Hare, Michael; Heuer, Annie; Chmielewska, Natalia; Gordon, Harper; Chandrahas, Anita S; Gonzalez-Buendia, Lucia; Delgado-Tirado, Santiago; Doan, Tri H; Vanderleest, Timothy E; Arevalo-Alquichire, Said; Obar, Robert A; Ortiz-Cordero, Carolina; Villegas, Andres; Sepulveda-Falla, Diego; Kim, Leo A; Lopera, Francisco; Mahley, Robert; Huang, Yadong; Quiroz, Yakeel T; Arboleda-Velasquez, Joseph F.

in: ALZHEIMERS DEMENT, Jahrgang 20, Nr. 2, 02.2024, S. 819-836.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Marino, C, Perez-Corredor, P, O'Hare, M, Heuer, A, Chmielewska, N, Gordon, H, Chandrahas, AS, Gonzalez-Buendia, L, Delgado-Tirado, S, Doan, TH, Vanderleest, TE, Arevalo-Alquichire, S, Obar, RA, Ortiz-Cordero, C, Villegas, A, Sepulveda-Falla, D, Kim, LA, Lopera, F, Mahley, R, Huang, Y, Quiroz, YT & Arboleda-Velasquez, JF 2024, 'APOE Christchurch-mimetic therapeutic antibody reduces APOE-mediated toxicity and tau phosphorylation', ALZHEIMERS DEMENT, Jg. 20, Nr. 2, S. 819-836. https://doi.org/10.1002/alz.13436

APA

Marino, C., Perez-Corredor, P., O'Hare, M., Heuer, A., Chmielewska, N., Gordon, H., Chandrahas, A. S., Gonzalez-Buendia, L., Delgado-Tirado, S., Doan, T. H., Vanderleest, T. E., Arevalo-Alquichire, S., Obar, R. A., Ortiz-Cordero, C., Villegas, A., Sepulveda-Falla, D., Kim, L. A., Lopera, F., Mahley, R., ... Arboleda-Velasquez, J. F. (2024). APOE Christchurch-mimetic therapeutic antibody reduces APOE-mediated toxicity and tau phosphorylation. ALZHEIMERS DEMENT, 20(2), 819-836. https://doi.org/10.1002/alz.13436

Vancouver

Marino C, Perez-Corredor P, O'Hare M, Heuer A, Chmielewska N, Gordon H et al. APOE Christchurch-mimetic therapeutic antibody reduces APOE-mediated toxicity and tau phosphorylation. ALZHEIMERS DEMENT. 2024 Feb;20(2):819-836. https://doi.org/10.1002/alz.13436

Bibtex

@article{98d10a906b014bcbb76f61fb3e2e644d,
title = "APOE Christchurch-mimetic therapeutic antibody reduces APOE-mediated toxicity and tau phosphorylation",
abstract = "INTRODUCTION: We discovered that the APOE3 Christchurch (APOE3Ch) variant may provide resistance to Alzheimer's disease (AD). This resistance may be due to reduced pathological interactions between ApoE3Ch and heparan sulfate proteoglycans (HSPGs).METHODS: We developed and characterized the binding, structure, and preclinical efficacy of novel antibodies targeting human ApoE-HSPG interactions.RESULTS: We found that one of these antibodies, called 7C11, preferentially bound ApoE4, a major risk factor for sporadic AD, and disrupts heparin-ApoE4 interactions. We also determined the crystal structure of a Fab fragment of 7C11 and used computer modeling to predict how it would bind to ApoE. When we tested 7C11 in mouse models, we found that it reduced recombinant ApoE-induced tau pathology in the retina of MAPT*P301S mice and curbed pTau S396 phosphorylation in brains of systemically treated APOE4 knock-in mice. Targeting ApoE-HSPG interactions using 7C11 antibody may be a promising approach to developing new therapies for AD.",
author = "Claudia Marino and Paula Perez-Corredor and Michael O'Hare and Annie Heuer and Natalia Chmielewska and Harper Gordon and Chandrahas, {Anita S} and Lucia Gonzalez-Buendia and Santiago Delgado-Tirado and Doan, {Tri H} and Vanderleest, {Timothy E} and Said Arevalo-Alquichire and Obar, {Robert A} and Carolina Ortiz-Cordero and Andres Villegas and Diego Sepulveda-Falla and Kim, {Leo A} and Francisco Lopera and Robert Mahley and Yadong Huang and Quiroz, {Yakeel T} and Arboleda-Velasquez, {Joseph F}",
note = "{\textcopyright} 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.",
year = "2024",
month = feb,
doi = "10.1002/alz.13436",
language = "English",
volume = "20",
pages = "819--836",
journal = "ALZHEIMERS DEMENT",
issn = "1552-5260",
publisher = "Elsevier Inc.",
number = "2",

}

RIS

TY - JOUR

T1 - APOE Christchurch-mimetic therapeutic antibody reduces APOE-mediated toxicity and tau phosphorylation

AU - Marino, Claudia

AU - Perez-Corredor, Paula

AU - O'Hare, Michael

AU - Heuer, Annie

AU - Chmielewska, Natalia

AU - Gordon, Harper

AU - Chandrahas, Anita S

AU - Gonzalez-Buendia, Lucia

AU - Delgado-Tirado, Santiago

AU - Doan, Tri H

AU - Vanderleest, Timothy E

AU - Arevalo-Alquichire, Said

AU - Obar, Robert A

AU - Ortiz-Cordero, Carolina

AU - Villegas, Andres

AU - Sepulveda-Falla, Diego

AU - Kim, Leo A

AU - Lopera, Francisco

AU - Mahley, Robert

AU - Huang, Yadong

AU - Quiroz, Yakeel T

AU - Arboleda-Velasquez, Joseph F

N1 - © 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

PY - 2024/2

Y1 - 2024/2

N2 - INTRODUCTION: We discovered that the APOE3 Christchurch (APOE3Ch) variant may provide resistance to Alzheimer's disease (AD). This resistance may be due to reduced pathological interactions between ApoE3Ch and heparan sulfate proteoglycans (HSPGs).METHODS: We developed and characterized the binding, structure, and preclinical efficacy of novel antibodies targeting human ApoE-HSPG interactions.RESULTS: We found that one of these antibodies, called 7C11, preferentially bound ApoE4, a major risk factor for sporadic AD, and disrupts heparin-ApoE4 interactions. We also determined the crystal structure of a Fab fragment of 7C11 and used computer modeling to predict how it would bind to ApoE. When we tested 7C11 in mouse models, we found that it reduced recombinant ApoE-induced tau pathology in the retina of MAPT*P301S mice and curbed pTau S396 phosphorylation in brains of systemically treated APOE4 knock-in mice. Targeting ApoE-HSPG interactions using 7C11 antibody may be a promising approach to developing new therapies for AD.

AB - INTRODUCTION: We discovered that the APOE3 Christchurch (APOE3Ch) variant may provide resistance to Alzheimer's disease (AD). This resistance may be due to reduced pathological interactions between ApoE3Ch and heparan sulfate proteoglycans (HSPGs).METHODS: We developed and characterized the binding, structure, and preclinical efficacy of novel antibodies targeting human ApoE-HSPG interactions.RESULTS: We found that one of these antibodies, called 7C11, preferentially bound ApoE4, a major risk factor for sporadic AD, and disrupts heparin-ApoE4 interactions. We also determined the crystal structure of a Fab fragment of 7C11 and used computer modeling to predict how it would bind to ApoE. When we tested 7C11 in mouse models, we found that it reduced recombinant ApoE-induced tau pathology in the retina of MAPT*P301S mice and curbed pTau S396 phosphorylation in brains of systemically treated APOE4 knock-in mice. Targeting ApoE-HSPG interactions using 7C11 antibody may be a promising approach to developing new therapies for AD.

U2 - 10.1002/alz.13436

DO - 10.1002/alz.13436

M3 - SCORING: Journal article

C2 - 37791598

VL - 20

SP - 819

EP - 836

JO - ALZHEIMERS DEMENT

JF - ALZHEIMERS DEMENT

SN - 1552-5260

IS - 2

ER -