Telomere Shortening in the Alzheimer's Disease Neuroimaging Initiative Cohort.

ABSTRACT: BACKGROUND:Although shorter telomeres have been associated with Alzheimer's disease (AD), it is unclear whether longitudinal change in telomere length is associated with AD progression. OBJECTIVE:To investigate the association of telomere length change with AD diagnosis and progression. METHODS:In 653 individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort, T/S ratio (telomere versus single copy gene), a proxy of telomere length, was measured for up to five visits per participant (N?=?1918 samples post-QC) using quantitative PCR (qPCR). T/S ratio was adjusted for batch effects and DNA storage time. A mixed effects model was used to evaluate association of telomere length with AD diagnostic group and interaction of age and diagnosis. Another mixed effects model was used to compare T/S ratio changes pre- to post-conversion to MCI or AD to telomere change in participants with stable diagnoses. RESULTS:Shorter telomeres were associated with older age (Effect Size (ES)?=?-0.23) and male sex (ES?=?-0.26). Neither baseline T/S ratio (ES?=?-0.036) nor T/S ratio change (ES?=?0.046) differed significantly between AD diagnostic groups. MCI/AD converters showed greater, but non-significant, telomere shortening compared to non-converters (ES?=?-0.186). CONCLUSIONS:Although AD compared to controls showed small, non-significant effects for baseline T/S ratio and T/S ratio shortening, we did observe a larger, though still non-significant effect for greater telomere shortening in converters compared to non-converters. Although our results do not support telomere shortening as a robust biomarker of AD progression, further investigation in larger samples and for subgroups of participants may be informative.

SUBMITTER: Nudelman KNH 

PROVIDER: S-EPMC7481955 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature