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Title: Genetically predicted telomere length and Alzheimer’s disease endophenotypes: a Mendelian randomization study
Author: 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
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 Gomez, Cleofé
Polo, Albina
Pradas, Sandra
Salvadó, Gemma
Shekari, Mahnaz
Soteras, Anna
Stankeviciute, Laura
Vilanova, Marc
The Alfa Study
Keywords: Malaltia d'Alzheimer
Alzheimer's disease
Issue Date: 7-Nov-2022
Publisher: Springer Science and Business Media LLC
Abstract: 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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It is part of: Alzheimer's Research & Therapy, 2022, vol. 14, núm. 167
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ISSN: 1758-9193
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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