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ORIGINAL RESEARCH article
Front. Aging Neurosci.
Sec. Alzheimer's Disease and Related Dementias
Volume 17 - 2025 | doi: 10.3389/fnagi.2025.1557016
Leukocyte Telomere Attrition in Cognitive Decline: Associations with APOE Genotype and Cardiovascular Risk Factors
Provisionally accepted
Alexandre Guimarães De Almeida Barros 1
Thayana Oliveira SOares 1 Ariane Flávia Almeida Lage 1
Marco Túlio Gualberto Cintra 1
Jonas Jardim de Paula 1 Olívio Brito Malheiro 1 Antonio Eiras Falcao 2 Christiano Altamiro Coli Nogueira 3 Leandro Braz de Carvalho 3
Marco Aurelio Romano-Silva 1
Debora Marques Miranda 1 Bernardo de Mattos Viana 1
Daniela Valadão Rosa 1
Maria Aparecida Bicalho 1*- 1 Federal University of Minas Gerais, Belo Horizonte, Brazil
- 2 State University of Campinas, Campinas, São Paulo, Brazil
- 3 Unimed BH - Hospital Unimed Contorno, Belo Horizonte, Brazil
Telomere shortening represents a fundamental mechanism of cellular aging potentially implicated in neurodegenerative processes. This study investigated the complex associations among leukocyte telomere length, cardiovascular risk profiles, and APOE polymorphisms in age-related cognitive decline.Through a cross-sectional analysis of 90 participants stratified by cognitive status into three groups: cognitively unimpaired (CU), mild cognitive impairment (MCI), and Alzheimer's Disease (AD), we quantified relative telomere length using quantitative PCR, performed APOE genotyping and assessed cardiovascular risk factors. Quantitative analysis revealed significantly reduced telomere length in the AD group compared to CU and MCI groups. Multivariate regression analysis identified cognitive status as an independent predictor of telomere length (β = -0.468, p < 0.001). APOE ε4 carrier status showed higher prevalence in AD subjects as expected. Cardiovascular risk factors demonstrated no significant correlation with telomere length across cognitive groups. Our findings establish a robust association between telomere shortening and advanced cognitive impairment in AD, suggesting potential utility as a neurodegenerative biomarker. This relationship appears independent of traditional cardiovascular risk factors, highlighting the complexity of cellular aging mechanisms in neurodegeneration.
Keywords: telomere attrition, Aging, Alzheimer´s disease, cognitive decline, Neurodegenarative disease
Received: 07 Jan 2025; Accepted: 20 Mar 2025.
Copyright: © 2025 Barros, SOares, Lage, Cintra, de Paula, Malheiro, Falcao, Nogueira, Carvalho, Romano-Silva, Miranda, Viana, Rosa and Bicalho. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Maria Aparecida Bicalho, Federal University of Minas Gerais, Belo Horizonte, Brazil
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