Genetically predicted telomere length and Alzheimer’s disease endophenotypes: a Mendelian randomization study

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 signat...

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Detalles Bibliográficos
Autores: Rodríguez Fernández, Blanca, Vilor Tejedor, Natalia, Arenaza Urquijo, Eider M., Sánchez Benavides, Gonzalo, Suárez Calvet, Marc, Operto, Grégory, Minguillón, Carolina, Fauria, Karine, Kollmorgen, Gwendlyn, Suridjan, Ivonne, Castro de Moura, Manuel, Piñeyro, David, Esteller, Manel, 1968-, Blennow, Kaj, Zetterberg, Henrik, Vivo, Immaculata de, Molinuevo, José Luis, Navarro, Arcadi, Gispert, Juan Domingo, Sala Vila, Aleix, Crous Bou, Marta, Akinci, Müge, Beteta, Annabella, Brugulat Serrat, Anna, Cacciaglia, Raffaele, Cañas, Alba, Cumplido, Irene, Deulofeu, Carme, Dominguez, Ruth, Emilio, Maria, Falcon, Carles, Fuentes, Sherezade, Grau Rivera, Oriol, González de Echávarri, José M., Hernandez, Laura, Genius, Patricia, Huesa, Gema, Huguet, Jordi, Palacios, Eva M., Marne, Paula, Menchón, Tania, Milà Alomà, Marta, Peña-Gómez, Cleofé, Polo, Albina, Pradas, Sandra, Salvadó, Gemma, Shekari, Mahnaz, Soteras, Anna, Stankeviciute, Laura, Vilanova, Marc, The Alfa Study
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/191362
Acceso en línea:https://hdl.handle.net/2445/191362
Access Level:acceso abierto
Palabra clave:Malaltia d'Alzheimer
Telòmer
Alzheimer's disease
Telomere
Descripción
Sumario: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-epsilon 4 status and polygenic risk score of AD were conducted. MR analysis revealed significant associations between genetically predicted longer TL and lower levels of CSF A beta and higher levels of CSF NfL only in APOE-epsilon 4 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.

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