Telomere Shortening in the Alzheimer's Disease Neuroimaging Initiative Cohort

Overview

Journal J Alzheimers Dis

Publisher Sage Publications

Specialties Geriatrics
Neurology

Date 2019 Jul 20

PMID 31322561

Citations 9

Authors

Kelly N H Nudelman

Jue Lin

Kathleen A Lane

Kwangsik Nho

Sungeun Kim

Kelley M Faber

Shannon L Risacher

Tatiana M Foroud

Sujuan Gao

Justin W Davis

Michael W Weiner

Andrew J Saykin

Affiliations

Soon will be listed here.

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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References

Horgusluoglu E, Nudelman K, Nho K, Saykin A . Adult neurogenesis and neurodegenerative diseases: A systems biology perspective. Am J Med Genet B Neuropsychiatr Genet. 2016; 174(1):93-112. PMC: 4987273. DOI: 10.1002/ajmg.b.32429. View

Lu W, Zhang Y, Liu D, Songyang Z, Wan M . Telomeres-structure, function, and regulation. Exp Cell Res. 2012; 319(2):133-41. PMC: 4051234. DOI: 10.1016/j.yexcr.2012.09.005. View

Saliques S, Teyssier J, Vergely C, Lorgis L, Lorin J, Farnier M . Circulating leukocyte telomere length and oxidative stress: a new target for statin therapy. Atherosclerosis. 2011; 219(2):753-60. DOI: 10.1016/j.atherosclerosis.2011.09.011. View

Pawlas N, Plachetka A, Kozlowska A, Broberg K, Kasperczyk S . Telomere length in children environmentally exposed to low-to-moderate levels of lead. Toxicol Appl Pharmacol. 2015; 287(2):111-118. DOI: 10.1016/j.taap.2015.05.005. View

Park J, Venteicher A, Hong J, Choi J, Jun S, Shkreli M . Telomerase modulates Wnt signalling by association with target gene chromatin. Nature. 2009; 460(7251):66-72. PMC: 4349391. DOI: 10.1038/nature08137. View

Jenkins E, Ye L, Krinsky-McHale S, Zigman W, Schupf N, Silverman W . Telomere longitudinal shortening as a biomarker for dementia status of adults with Down syndrome. Am J Med Genet B Neuropsychiatr Genet. 2015; 171B(2):169-74. DOI: 10.1002/ajmg.b.32389. View

Lin J, Epel E, Cheon J, Kroenke C, Sinclair E, Bigos M . Analyses and comparisons of telomerase activity and telomere length in human T and B cells: insights for epidemiology of telomere maintenance. J Immunol Methods. 2009; 352(1-2):71-80. PMC: 3280689. DOI: 10.1016/j.jim.2009.09.012. View

Tucker L . Dietary Fiber and Telomere Length in 5674 U.S. Adults: An NHANES Study of Biological Aging. Nutrients. 2018; 10(4). PMC: 5946185. DOI: 10.3390/nu10040400. View

Levy M, Allsopp R, Futcher A, Greider C, Harley C . Telomere end-replication problem and cell aging. J Mol Biol. 1992; 225(4):951-60. DOI: 10.1016/0022-2836(92)90096-3. View

10.

Eisenberg D . Inconsistent inheritance of telomere length (TL): is offspring TL more strongly correlated with maternal or paternal TL?. Eur J Hum Genet. 2013; 22(1):8-9. PMC: 3865394. DOI: 10.1038/ejhg.2013.202. View

11.

Kang H, Choi Y, Hong S, Kim K, Woo R, Won S . Ectopic expression of the catalytic subunit of telomerase protects against brain injury resulting from ischemia and NMDA-induced neurotoxicity. J Neurosci. 2004; 24(6):1280-7. PMC: 6730349. DOI: 10.1523/JNEUROSCI.4082-03.2004. View

12.

Holohan B, Wright W, Shay J . Cell biology of disease: Telomeropathies: an emerging spectrum disorder. J Cell Biol. 2014; 205(3):289-99. PMC: 4018777. DOI: 10.1083/jcb.201401012. View

13.

Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View

14.

Ridout K, Levandowski M, Ridout S, Gantz L, Goonan K, Palermo D . Early life adversity and telomere length: a meta-analysis. Mol Psychiatry. 2017; 23(4):858-871. PMC: 5608639. DOI: 10.1038/mp.2017.26. View

15.

Muezzinler A, Zaineddin A, Brenner H . A systematic review of leukocyte telomere length and age in adults. Ageing Res Rev. 2013; 12(2):509-19. DOI: 10.1016/j.arr.2013.01.003. View

16.

Hinterberger M, Fischer P, Huber K, Krugluger W, Zehetmayer S . Leukocyte telomere length is linked to vascular risk factors not to Alzheimer's disease in the VITA study. J Neural Transm (Vienna). 2017; 124(7):809-819. DOI: 10.1007/s00702-017-1721-z. View

17.

Cawthon R . Telomere measurement by quantitative PCR. Nucleic Acids Res. 2002; 30(10):e47. PMC: 115301. DOI: 10.1093/nar/30.10.e47. View

18.

Masutomi K, Possemato R, Wong J, Currier J, Tothova Z, Manola J . The telomerase reverse transcriptase regulates chromatin state and DNA damage responses. Proc Natl Acad Sci U S A. 2005; 102(23):8222-7. PMC: 1149439. DOI: 10.1073/pnas.0503095102. View

19.

Eisenberg D, Hayes M, Kuzawa C . Delayed paternal age of reproduction in humans is associated with longer telomeres across two generations of descendants. Proc Natl Acad Sci U S A. 2012; 109(26):10251-6. PMC: 3387085. DOI: 10.1073/pnas.1202092109. View

20.

Leung C, Laraia B, Needham B, Rehkopf D, Adler N, Lin J . Soda and cell aging: associations between sugar-sweetened beverage consumption and leukocyte telomere length in healthy adults from the National Health and Nutrition Examination Surveys. Am J Public Health. 2014; 104(12):2425-31. PMC: 4229419. DOI: 10.2105/AJPH.2014.302151. View