Kelly N H Nudelman1,2,3, Jue Lin4, Kathleen A Lane5, Kwangsik Nho3,6, Sungeun Kim6,7, Kelley M Faber1,2, Shannon L Risacher3,6, Tatiana M Foroud1,2,3, Sujuan Gao5, Justin W Davis8, Michael W Weiner9, Andrew J Saykin1,3,6. 1. Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA. 2. National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD), Indiana University School of Medicine, Indianapolis, IN, USA. 3. Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA. 4. Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA. 5. Biostatistics, Indiana University School of Medicine, Indianapolis, IN, USA. 6. Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA. 7. Electrical and Computer Engineering, SUNY Oswego, Oswego, NY, USA. 8. Genomics Research Center, AbbVie, North Chicago, IL, USA. 9. Center for Imaging of Neurodegenerative Diseases, Department of Radiology, San Francisco VA Medical Center/University of California San Francisco, San Francisco, CA, USA.
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.
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.
Authors: Edmund C Jenkins; Lingling Ye; Sharon J Krinsky-McHale; Warren B Zigman; Nicole Schupf; Wayne P Silverman Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2015-11-23 Impact factor: 3.568
Authors: Emrin Horgusluoglu; Kelly Nudelman; Kwangsik Nho; Andrew J Saykin Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2016-02-16 Impact factor: 3.568
Authors: Jae-Il Park; Andrew S Venteicher; Ji Yeon Hong; Jinkuk Choi; Sohee Jun; Marina Shkreli; Woody Chang; Zhaojing Meng; Peggie Cheung; Hong Ji; Margaret McLaughlin; Timothy D Veenstra; Roel Nusse; Pierre D McCrea; Steven E Artandi Journal: Nature Date: 2009-07-02 Impact factor: 49.962
Authors: Bo-Hyun Kim; Aparna Vasanthakumar; Qingqin S Li; Kelly N H Nudelman; Shannon L Risacher; Justin W Davis; Kenneth Idler; Jong-Min Lee; Sang Won Seo; Jeffrey F Waring; Andrew J Saykin; Kwangsik Nho Journal: Alzheimers Dement (Amst) Date: 2022-09-20
Authors: Emily R Mahoney; Logan Dumitrescu; Mabel Seto; Kelly N H Nudelman; Rachel F Buckley; Katie A Gifford; Andrew J Saykin; Angela J Jefferson; Timothy J Hohman Journal: Alzheimers Dement (N Y) Date: 2019-12-09