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Get Free AccessAbstract Telomere length (TL) is associated with biological aging, consequently influencing the risk of age-related diseases such as Alzheimer’s disease (AD). We aimed to evaluate the potential causal role of TL in AD endophenotypes (i.e . , cognitive performance, N = 2233; brain age and AD-related signatures, N = 1134; and cerebrospinal fluid biomarkers (CSF) of AD and neurodegeneration, N = 304) through a Mendelian randomization (MR) analysis. Our analysis was conducted in the context of the ALFA (ALzheimer and FAmilies) study, a population of cognitively healthy individuals at risk of AD. A total of 20 single nucleotide polymorphisms associated with TL were used to determine the effect of TL on AD endophenotypes. Analyses were adjusted by age, sex, and years of education. Stratified analyses by APOE -ɛ4 status and polygenic risk score of AD were conducted. MR analysis revealed significant associations between genetically predicted longer TL and lower levels of CSF Aβ and higher levels of CSF NfL only in APOE -ɛ4 non-carriers. Moreover, inheriting longer TL was associated with greater cortical thickness in age and AD-related brain signatures and lower levels of CSF p-tau among individuals at a high genetic predisposition to AD. Further observational analyses are warranted to better understand these associations. Graphical Abstract
Blanca Rodríguez‐Fernández, Natàlia Vilor‐Tejedor, Eider M. Arenaza‐Urquijo, Gonzalo Sánchez‐Benavides, Marc Suárez‐Calvet, Grégory Operto, Carolina Minguillón, Karine Fauria, Gwendlyn Kollmorgen, Ivonne Suridjan, Manuel Castro de Moura, David Piñeyro, Manel Esteller, Kaj Blennow, Henrik Zetterberg, Immaculata De Vivo, José Luís Molinuevo, Arcadi Navarro, Juan Domingo Gispert, Aleix Sala‐Vila, Marta Crous‐Bou, Müge Akinci, Annabella Beteta, Anna Brugulat‐Serrat, Raffaele Cacciaglia, Alba Cañas, Irene Cumplido, Carme Deulofeu, Ruth Dominguez, Maria Emilio, Carles Falcón, Sherezade Fuentes, Oriol Grau‐Rivera, José María Gónzalez‐de‐Echávarri, Laura L. Hernandez, Patricia Genius, Gema Huesa, Jordi Huguet, Eva Palacios, Paula Marne, Tania Menchón, Marta Milà‐Alomà, Cleofé Peña-Gómez, Albina Polo, Sandra Pradas, Gemma Salvadó, Mahnaz Shekari, Anna Soteras, Laura Stankeviciute, Marc Vilanova (2022). Genetically predicted telomere length and Alzheimer’s disease endophenotypes: a Mendelian randomization study. , 14(1), DOI: https://doi.org/10.1186/s13195-022-01101-9.
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Type
Article
Year
2022
Authors
50
Datasets
0
Total Files
0
Language
en
DOI
https://doi.org/10.1186/s13195-022-01101-9
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