Telomere Shortening in the Alzheimer's Disease Neuroimaging Initiative Cohort

Kelly N.H. Nudelman, Jue Lin, Kathleen A. Lane, Kwangsik Nho, Sungeun Kim, Kelley M. Faber, Shannon L. Risacher, Tatiana Foroud, Sujuan Gao, Justin W. Davis, Michael W. Weiner, Andrew Saykin

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)33-43
Number of pages11
JournalJournal of Alzheimer's Disease
Volume71
Issue number1
DOIs
StatePublished - Jan 1 2019

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Telomere Shortening
Neuroimaging
Telomere
Alzheimer Disease
Disease Progression
Proxy
Age Groups
Biomarkers

Keywords

  • Alzheimer's disease
  • longitudinal
  • progression
  • shortening
  • telomere

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Cite this

Telomere Shortening in the Alzheimer's Disease Neuroimaging Initiative Cohort. / Nudelman, Kelly N.H.; Lin, Jue; Lane, Kathleen A.; Nho, Kwangsik; Kim, Sungeun; Faber, Kelley M.; Risacher, Shannon L.; Foroud, Tatiana; Gao, Sujuan; Davis, Justin W.; Weiner, Michael W.; Saykin, Andrew.

In: Journal of Alzheimer's Disease, Vol. 71, No. 1, 01.01.2019, p. 33-43.

Research output: Contribution to journalArticle

Nudelman, KNH, Lin, J, Lane, KA, Nho, K, Kim, S, Faber, KM, Risacher, SL, Foroud, T, Gao, S, Davis, JW, Weiner, MW & Saykin, A 2019, 'Telomere Shortening in the Alzheimer's Disease Neuroimaging Initiative Cohort', Journal of Alzheimer's Disease, vol. 71, no. 1, pp. 33-43. https://doi.org/10.3233/JAD-190010
Nudelman, Kelly N.H. ; Lin, Jue ; Lane, Kathleen A. ; Nho, Kwangsik ; Kim, Sungeun ; Faber, Kelley M. ; Risacher, Shannon L. ; Foroud, Tatiana ; Gao, Sujuan ; Davis, Justin W. ; Weiner, Michael W. ; Saykin, Andrew. / Telomere Shortening in the Alzheimer's Disease Neuroimaging Initiative Cohort. In: Journal of Alzheimer's Disease. 2019 ; Vol. 71, No. 1. pp. 33-43.
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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.",
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AU - Lin, Jue

AU - Lane, Kathleen A.

AU - Nho, Kwangsik

AU - Kim, Sungeun

AU - Faber, Kelley M.

AU - Risacher, Shannon L.

AU - Foroud, Tatiana

AU - Gao, Sujuan

AU - Davis, Justin W.

AU - Weiner, Michael W.

AU - Saykin, Andrew

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N2 - 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.

AB - 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.

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