Long‐Read Sequencing Reveals Ancestral intragenic <i>APOE</i> Haplotypes with Distinct Roles in Alzheimer’s Disease

This study redefines the human APOE ε3 and ε4 alleles as genetically heterogeneous entities. Using ONT long-read sequencing, we achieved high-resolution mapping of intragenic haplotypic structure and regulatory variation previously obscured by conventional approaches. This enabled the identification of ancestral haplotypes with distinct functional profiles and potential relevance to Alzheimer's disease pathogenesis. These findings highlight the importance of incorporating haplotype-level resolution into Alzheimer's risk assessment, therapeutic targeting, and precision medicine strategies.

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Publication Details

Journal
Alzheimer s & Dementia
Published
2025-12-01
DOI
https://doi.org/10.1002/alz70861_108005
Primary Topic
Alzheimer's disease research and treatments
Type
article
Field-Weighted Citation Impact
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article

Long‐Read Sequencing Reveals Ancestral intragenic APOE Haplotypes with Distinct Roles in Alzheimer’s Disease

Maitée Rosende‐Roca, Montserrat Alegret, C. Olive, José E Cavazos et al.
Alzheimer s & Dementia
Alzheimer's disease research and treatments
article

Long‐Read Sequencing Reveals Ancestral intragenic APOE Haplotypes with Distinct Roles in Alzheimer’s Disease

Maitée Rosende‐Roca, Montserrat Alegret, C. Olive, José E Cavazos, María Eugenia Sáez, Arcadi Segura i Navarro, Pablo García‐González, Pilar Sánz, Victoria M. Fernandez, Agustín Ruiz, Marta Marquié, Frederic Brosseron, Alfredo Ramirez, Michael T. Heneka, Alfredo Cabrera Socorro, Raquel Puerta, Lluís Tárraga, Amanda Cano, Mercè Boada, Sergi Valero, Itziar de Rojas, Pamela Martino‐Adami
article en

Abstract

This study redefines the human APOE ε3 and ε4 alleles as genetically heterogeneous entities. Using ONT long-read sequencing, we achieved high-resolution mapping of intragenic haplotypic structure and regulatory variation previously obscured by conventional approaches. This enabled the identification of ancestral haplotypes with distinct functional profiles and potential relevance to Alzheimer's disease pathogenesis. These findings highlight the importance of incorporating haplotype-level resolution into Alzheimer's risk assessment, therapeutic targeting, and precision medicine strategies.

Alzheimer s & DementiaVol. 21(S7)
Southwest Research Institute (US), Janssen (Belgium) (BE), The University of Texas at San Antonio Health Science Center (US), University of Cologne (DE), University of Luxembourg (LU), Instituto de Salud Carlos III (ES), German Center for Neurodegenerative Diseases (DE), Universitat Internacional de Catalunya (ES), Biomedical Research Networking Center on Neurodegenerative Diseases (ES), Centro Andaluz de Biología del Desarrollo (ES), Fundació ACE (ES), Barcelonaβeta Brain Research Center (ES), University Hospital Cologne (DE), The University of Texas Health Science Center at Houston (US)
Openalex Percentile: Top 34%
Alzheimer's disease research and treatments
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