Mitochondrial methylcytosines as blood-based biomarkers for Alzheimer's disease dementia prognosis
Alzheimer's Disease Dementia (ADD) prognosis is an unmet medical need. Mitochondrial dysfunction is an early AD etiopathogenic factor. The present study analyzed mitochondrial DNA (mtDNA) methylation patterns in blood samples from patients with mild cognitive impairment (MCI) who progressed to...
| Autores: | , , , , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/224918 |
| Acceso en línea: | https://hdl.handle.net/2445/224918 |
| Access Level: | acceso abierto |
| Palabra clave: | ADN mitocondrial Malaltia d'Alzheimer Neurociències Metilació Neurologia Mitochondrial DNA Alzheimer's disease Neurosciences Methylation Neurology |
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Mitochondrial methylcytosines as blood-based biomarkers for Alzheimer's disease dementia prognosisGascón-Bayarri, JordiMosquera Mayo, José LuísBlanch Lozano, MartaMartí Benaiges, PauFontal Aina, BeatrizTrapero Candela, CarlaRojo Fité, NuriaRico, InmaCampdelacreu i Fumadó, JaumeFowler, CristopherLaws, Simon M.Tort Merino, AdriàSánchez del Valle Díaz, RaquelBello, JoanFortea Ormaechea, JuanLleó Bisa, AlbertoMehanian, CouroshSwerdlow, Russell H.Reñé Ramírez, RamonBarrachina, MartaADN mitocondrialMalaltia d'AlzheimerNeurociènciesMetilacióNeurologiaMitochondrial DNAAlzheimer's diseaseNeurosciencesMethylationNeurologyAlzheimer's Disease Dementia (ADD) prognosis is an unmet medical need. Mitochondrial dysfunction is an early AD etiopathogenic factor. The present study analyzed mitochondrial DNA (mtDNA) methylation patterns in blood samples from patients with mild cognitive impairment (MCI) who progressed to ADD (P), MCI remained stable (NP), and Cognitively Normal (CN) individuals. Differentially methylated sites were identified in the D-loop region in both CN vs. NP and NP vs. P comparisons, even before β-amyloid positivity. A Random Forest model was developed using mtDNA methylation data combined with cognitive and risk factor features. Model's performance was assessed by cross-validation and tested on an independent set, achieving 84.4% accuracy in training and 83.2% (95% CI: 75.2%-89.4%) in testing. For identifying P patients, sensitivity and specificity were 95.1% and 70.7%, respectively. The AUC-ROC was 90.3%. The developed model demonstrates predictive capacity in distinguishing cognitive decline and stability in MCI individuals, independently of their β-amyloid status.Elsevier2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/224918Articles publicats en revistes (Medicina)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1016/j.isci.2025.113418iScience, 2025, vol. 28, num. 9, 113418https://doi.org/10.1016/j.isci.2025.113418cc-by-nc-nd (c) Gascón-Bayarri, Jordi. et al., 2025http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2249182026-05-27T06:46:51Z |
| dc.title.none.fl_str_mv |
Mitochondrial methylcytosines as blood-based biomarkers for Alzheimer's disease dementia prognosis |
| title |
Mitochondrial methylcytosines as blood-based biomarkers for Alzheimer's disease dementia prognosis |
| spellingShingle |
Mitochondrial methylcytosines as blood-based biomarkers for Alzheimer's disease dementia prognosis Gascón-Bayarri, Jordi ADN mitocondrial Malaltia d'Alzheimer Neurociències Metilació Neurologia Mitochondrial DNA Alzheimer's disease Neurosciences Methylation Neurology |
| title_short |
Mitochondrial methylcytosines as blood-based biomarkers for Alzheimer's disease dementia prognosis |
| title_full |
Mitochondrial methylcytosines as blood-based biomarkers for Alzheimer's disease dementia prognosis |
| title_fullStr |
Mitochondrial methylcytosines as blood-based biomarkers for Alzheimer's disease dementia prognosis |
| title_full_unstemmed |
Mitochondrial methylcytosines as blood-based biomarkers for Alzheimer's disease dementia prognosis |
| title_sort |
Mitochondrial methylcytosines as blood-based biomarkers for Alzheimer's disease dementia prognosis |
| dc.creator.none.fl_str_mv |
Gascón-Bayarri, Jordi Mosquera Mayo, José Luís Blanch Lozano, Marta Martí Benaiges, Pau Fontal Aina, Beatriz Trapero Candela, Carla Rojo Fité, Nuria Rico, Inma Campdelacreu i Fumadó, Jaume Fowler, Cristopher Laws, Simon M. Tort Merino, Adrià Sánchez del Valle Díaz, Raquel Bello, Joan Fortea Ormaechea, Juan Lleó Bisa, Alberto Mehanian, Courosh Swerdlow, Russell H. Reñé Ramírez, Ramon Barrachina, Marta |
| author |
Gascón-Bayarri, Jordi |
| author_facet |
Gascón-Bayarri, Jordi Mosquera Mayo, José Luís Blanch Lozano, Marta Martí Benaiges, Pau Fontal Aina, Beatriz Trapero Candela, Carla Rojo Fité, Nuria Rico, Inma Campdelacreu i Fumadó, Jaume Fowler, Cristopher Laws, Simon M. Tort Merino, Adrià Sánchez del Valle Díaz, Raquel Bello, Joan Fortea Ormaechea, Juan Lleó Bisa, Alberto Mehanian, Courosh Swerdlow, Russell H. Reñé Ramírez, Ramon Barrachina, Marta |
| author_role |
author |
| author2 |
Mosquera Mayo, José Luís Blanch Lozano, Marta Martí Benaiges, Pau Fontal Aina, Beatriz Trapero Candela, Carla Rojo Fité, Nuria Rico, Inma Campdelacreu i Fumadó, Jaume Fowler, Cristopher Laws, Simon M. Tort Merino, Adrià Sánchez del Valle Díaz, Raquel Bello, Joan Fortea Ormaechea, Juan Lleó Bisa, Alberto Mehanian, Courosh Swerdlow, Russell H. Reñé Ramírez, Ramon Barrachina, Marta |
| author2_role |
author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
ADN mitocondrial Malaltia d'Alzheimer Neurociències Metilació Neurologia Mitochondrial DNA Alzheimer's disease Neurosciences Methylation Neurology |
| topic |
ADN mitocondrial Malaltia d'Alzheimer Neurociències Metilació Neurologia Mitochondrial DNA Alzheimer's disease Neurosciences Methylation Neurology |
| description |
Alzheimer's Disease Dementia (ADD) prognosis is an unmet medical need. Mitochondrial dysfunction is an early AD etiopathogenic factor. The present study analyzed mitochondrial DNA (mtDNA) methylation patterns in blood samples from patients with mild cognitive impairment (MCI) who progressed to ADD (P), MCI remained stable (NP), and Cognitively Normal (CN) individuals. Differentially methylated sites were identified in the D-loop region in both CN vs. NP and NP vs. P comparisons, even before β-amyloid positivity. A Random Forest model was developed using mtDNA methylation data combined with cognitive and risk factor features. Model's performance was assessed by cross-validation and tested on an independent set, achieving 84.4% accuracy in training and 83.2% (95% CI: 75.2%-89.4%) in testing. For identifying P patients, sensitivity and specificity were 95.1% and 70.7%, respectively. The AUC-ROC was 90.3%. The developed model demonstrates predictive capacity in distinguishing cognitive decline and stability in MCI individuals, independently of their β-amyloid status. |
| publishDate |
2025 |
| dc.date.none.fl_str_mv |
2025 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
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https://hdl.handle.net/2445/224918 |
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https://hdl.handle.net/2445/224918 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Reproducció del document publicat a: https://doi.org/10.1016/j.isci.2025.113418 iScience, 2025, vol. 28, num. 9, 113418 https://doi.org/10.1016/j.isci.2025.113418 |
| dc.rights.none.fl_str_mv |
cc-by-nc-nd (c) Gascón-Bayarri, Jordi. et al., 2025 http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
cc-by-nc-nd (c) Gascón-Bayarri, Jordi. et al., 2025 http://creativecommons.org/licenses/by-nc-nd/4.0/ |
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openAccess |
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application/pdf |
| dc.publisher.none.fl_str_mv |
Elsevier |
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Elsevier |
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Articles publicats en revistes (Medicina) reponame:Dipòsit Digital de la UB instname:Universidad de Barcelona |
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Universidad de Barcelona |
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Dipòsit Digital de la UB |
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Dipòsit Digital de la UB |
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