Leukocyte telomere length in mild cognitive impairment and Alzheimer's disease patients.

Numerous studies have reported an association between shortened leukocyte telomere length (LTL) and increased risk of Alzheimer's disease (AD). In this study we investigated the relationship between LTL and AD development, including in the analysis patients with amnestic mild cognitive impairment (aMCI), a clinical entity considered prodromal of AD. LTL (T/S ratio) was measured in patients with AD (n=61) or aMCI (n=46), and compared with LTL of age-matched controls (n=56). Significant LTL differences were observed between controls, aMCI and AD patients (p<0.0001), with mean LTL values (±s.d) in the order: AD patients (0.70±0.15)<aMCI patients (0.80±0.14)<controls (0.88±0.15). A positive relationship (linear regression p=0.004) was observed between LTL and cognitive performance (measured by Mini Mental State Examination score). LTL did not differ by APOE genotype. The shortened LTL observed in AD patients appears to stem from progressive telomere erosion possibly correlated with the cognitive decline characterizing conversion from aMCI to AD. LTL reduction, indicating active cell proliferation, may reflect immune system involvement in AD pathogenesis.