| Title: | Association between leukocyte telomere length and neurodegenerative diseases: a prospective cohort in the UK Biobank |
| Journal: | Journal of Neurology |
| Published: | 11 Feb 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41670794/ |
| DOI: | https://doi.org/10.1007/s00415-025-13479-1 |
| URL: | https://link.springer.com/content/pdf/10.1007/s00415-025-13479-1.pdf |
Publication 18303
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Abstract
BackgroundThis study aims to investigate the association between leukocyte telomere length (LTL) and the risk of incident NDDs using a large-scale cohort from the UK Biobank.MethodsData from 459,902 subjects were analyzed using Cox proportional hazards models and machine learning (ML) algorithms to assess LTL's association with NDD risk.ResultsShorter LTL was associated with an increased risk of NDDs, including Alzheimer's disease (HR: 0.52, 95% CI 0.40-0.67, P < 0.001), dementia in AD (HR: 0.53, 95% CI 0.39-0.73, P < 0.001), unspecified dementia (HR: 0.74, 95% CI 0.58-0.95, P < 0.05), degenerative diseases of the nervous system (including other specified degenerative diseases such as circumscribed brain atrophy and senile degeneration of the brain) (HR: 0.62, 95% CI 0.45-0.84, P < 0.01), extrapyramidal and movement disorders (including other specified extrapyramidal and movement disorders such as a range of tremors, chorea, tics, and other abnormal involuntary movements) (HR: 0.63, 95% CI 0.48-0.82, P < 0.01), and mental and behavioral disorders due to use of alcohol (HR: 0.46, 95% CI 0.38-0.55, P < 0.001). Conversely, longer LTL was associated with a 3.71-fold increased risk of multiple sclerosis (MS) (HR: 3.71, 95% CI 1.91-7.18, P < 0.001). ML models confirmed the predictive value of LTL for NDDs.ConclusionShorter LTL increased the risk of several NDDs, while longer LTL paradoxically predisposed individuals to MS, especially in younger populations. ML models demonstrated strong potential for predicting NDD risks, enhancing our understanding of the role of telomeres in neurodegeneration.</p>
15 Keywords
- Aged
- Aged, 80 and over
- Biological Specimen Banks
- Cohort Studies
- Female
- Humans
- Leukocytes
- Machine Learning
- Male
- Middle Aged
- Neurodegenerative Diseases
- Prospective Studies
- Telomere
- UK Biobank
- United Kingdom
4 Authors
- Xiangting Chen
- Yueqing Huang
- Chunhua Zhao
- Min Huang
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