Nudelman, Kelly N. H.Lin, JueLane, Kathleen A.Nho, KwangsikKim, SungeunFaber, Kelley M.Risacher, Shannon L.Foroud, Tatiana M.Gao, SujuanDavis, Justin W.Weiner, Michael W.Saykin, Andrew J.Initiative for the Alzheimer’s Disease Neuroimaging2021-05-282021-05-282019-09-03Nudelman, K. N. H., Lin, J., Lane, K. A., Nho, K., Kim, S., Faber, K. M., Risacher, S. L., Foroud, T. M., Gao, S., Davis, J. W., Weiner, M. W., Saykin, A. J., & Initiative, for the A. D. N. (2019). Telomere Shortening in the Alzheimer’s Disease Neuroimaging Initiative Cohort. Journal of Alzheimer’s Disease, 71(1), 33–43. https://doi.org/10.3233/JAD-1900101387-2877https://hdl.handle.net/1805/26072BACKGROUND: 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 vs. 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.en-USTelomerelongitudinalshorteningAlzheimer’s diseaseprogressionArticle