# Leukocyte telomere attrition in cognitive decline: associations with APOE genotype and cardiovascular risk factors

## TL;DR

This study shows that shorter telomeres in white blood cells are linked to Alzheimer's disease, independent of heart-related risks.

## Contribution

The study identifies a strong, independent link between telomere shortening and Alzheimer's disease, suggesting a potential biomarker for cognitive decline.

## Key findings

- Telomere length was significantly reduced in Alzheimer’s Disease patients compared to cognitively unimpaired and MCI groups.
- Cognitive status was an independent predictor of telomere length, with a strong negative correlation.
- Cardiovascular risk factors did not significantly correlate with telomere length across cognitive groups.

## Abstract

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.

Summarizing the relationship between leukocyte telomere shortening and Alzheimer’s disease (AD). Telomere attrition, driven by mechanisms such as oxidative stress, chronic inflammation, and cellular senescence, contributes to neurodegeneration characteristic of AD pathology, including amyloid-β deposition and tau aggregation. Shorter telomeres are significantly associated with advanced cognitive impairment observed in AD patients. This highlights the potential of telomere length as part of a biomarker panel for cognitive decline and suggests telomere maintenance as a promising therapeutic target to mitigate neurodegeneration.