A BBRC team detects that a genetic predisposition to longer telomeres could have a protective effect against Alzheimer's disease

Two studies carried out by the Pasqual Maragall Foundation's research centre, the Barcelonaβeta Brain Research Center (BBRC), and which have included participants from the ALFA Study, promoted by the "la Caixa" Foundation, have evaluated the role of telomere length, considered a marker of biological age, in neurodegenerative disorders and the risk of suffering from Alzheimer's disease. The results of this research indicate that genetic variants associated with longer telomere length may be associated with a lower risk of developing Alzheimer's disease. These genetic variants were associated with lower levels of some Alzheimer's biomarkers, such as the p-tau protein, as well as increased cortical thickness in cognitively healthy people with a high genetic predisposition to the disease.

"Telomeres are repetitive DNA sequences located at the ends of chromosomes. Their main function is to protect them, to prevent them from wearing out or deteriorating," explains Blanca Rodríguez-Fernández, BBRC researcher and first author of both studies. "Over time, and each time a cell divides, telomeres shorten. For this reason, their length is considered an indicator of biological age," she adds.

The first study, published in the Computational and Structural Biotechnology Journal, suggests that genetic variants associated with longer telomeres may have a protective effect on the risk of developing Alzheimer's disease and that they are significantly associated with longer life expectancy.

In the second study, published in Alzheimer's Research & Therapy and in collaboration with the research team of the Institute for Biomedical Research at Bellvitge Hospital, this possible relationship has been analysed through brain, cognitive and cerebrospinal fluid biomarkers of Alzheimer's disease and neurodegeneration. This pioneering study used samples from participants in the ALFA Study, a cohort that includes a population of cognitively healthy individuals at risk of Alzheimer's disease. 

The main results of this research reveal significant associations between genetic variants that predict longer telomere length and lower levels of some Alzheimer's biomarkers, such as the ptau protein. In addition, inheriting longer telomeres has been associated with greater cortical thickness among people with a high genetic predisposition to Alzheimer's disease in the future.

As Natàlia Vilor-Tejedor, senior co-investigator of the study and leader of the BBRC Neurobiogenetics team explains, "genetic variants associated with longer telomere length could protect brain structure through multiple mechanisms, either in regions affected mainly by processes related to Alzheimer's disease or to ageing itself".

The continuation of these studies is key to understanding the role of telomere length in the development of Alzheimer's disease. As Dr. Marta Crous-Bou, collaborating researcher at the BBRC and co-leader of the project, points out, although the findings are positive, "these should be replicated in larger cohorts, including participants at different stages of disease development, as well as follow-up of ALFA study participants and additional observational analyses to better understand the results obtained and underlying biological mechanisms". 

Rodríguez-Fernández, B., Gispert, J. D., Guigo, R., Navarro, A., Vilor-Tejedor, N. & Crous-Bou, M. (2022b). Genetically predicted telomere length and its relationship with neurodegenerative diseases and life expectancy. Computational and Structural Biotechnology Journal, 20, 4251- 4256. https://doi.org/10.1016/j.csbj.2022.08.006 

Rodríguez-Fernández, B., Vilor-Tejedor, N., Arenaza-Urquijo, E. M., Sánchez-Benavides, G., Suárez-Calvet, M., Operto, G., Minguillón, C., Fauria, K., Kollmorgen, G., Suridjan, I., de Moura, M. C., Piñeyro, D., Esteller, M., Blennow, K., Zetterberg, H., De Vivo, I., Molinuevo, J. L., Navarro, A., Gispert, J. D., Sala-Vila, A, Crous-Bou M. (2022). Genetically predicted telomere length and Alzheimer’s disease endophenotypes: a Mendelian randomization study. Alzheimer’s Research & Therapy, 14(1). https://doi.org/10.1186/s13195-022-01101-9 

Every 3 seconds a new case of dementia is diagnosed worldwide, and it is currently estimated that 50 million people suffer from dementia, most of them due to Alzheimer's disease. In Spain, this figure translates into more than 900,000 people affected. With life expectancy on the rise, if no treatment is found to prevent or slow down the course of the disease, the number of cases could triple by 2050, reaching epidemic proportions, as the latest World Alzheimer Report 2018 published by Alzheimer's Disease International points out. 

Brain Research Center (BBRC) is the research centre of the Pasqual Maragall Foundation, promoted by the "la Caixa" Foundation since its creation, dedicated to the prevention of Alzheimer's disease and the study of cognitive functions affected in healthy and pathological ageing. The Pasqual Maragall Foundation is a non-profit organisation that was set up in April 2008 in response to the commitment made by Pasqual Maragall, former Mayor of Barcelona and former President of the Generalitat de Catalunya, when he publicly announced that he had been diagnosed with Alzheimer's disease. The Foundation's mission is to promote research to prevent Alzheimer's disease and to offer solutions that improve the quality of life of those affected and their carers.