Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/15838
Título
Genetically predicted telomere length and Alzheimer's disease endophenotypes: a Mendelian randomization study.
Autor(es)
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 | de Moura, Manuel Castro | Piñeyro, David | Esteller, Manel | Blennow, Kaj | Zetterberg, Henrik | De Vivo, Immaculata | Molinuevo, José Luis | Navarro, Arcadi | Gispert, Juan Domingo | Sala-Vila, Aleix CNIC | Crous-Bou, Marta
Fecha de publicación
2022-11-07
Cita
Alzheimers Res Ther. 2022 Nov 7;14(1):167
Idioma
Inglés
Tipo de documento
journal article
Resumen
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.
MESH
Alzheimer Disease | Humans | Mendelian Randomization Analysis | Endophenotypes | Biomarkers | Apolipoproteins E | Telomere | tau Proteins | Amyloid beta-Peptides
Versión en línea
DOI
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