Telomere Shortening in the Alzheimer’s Disease Neuroimaging Initiative Cohort
| Autor: | Nudelman Knh, Sujuan Gao, Andrew J. Saykin, Tatiana Foroud, Kathleen A. Lane, Kelley Faber, Michael W. Weiner, Shannon L. Risacher, Sungeun Kim, Kwangsik Nho, Jue Lin, Justin W. Davis |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Oncology medicine.medical_specialty Databases Factual Neuroimaging Disease Article 03 medical and health sciences Sex Factors 0302 clinical medicine Alzheimer Disease Single copy gene Internal medicine Humans Medicine Telomere Shortening Aged business.industry General Neuroscience Age Factors Telomere Homeostasis General Medicine Dna storage Telomere Psychiatry and Mental health Clinical Psychology 030104 developmental biology Real-time polymerase chain reaction Cohort Length change Disease Progression Female Geriatrics and Gerontology business 030217 neurology & neurosurgery Alzheimer's Disease Neuroimaging Initiative |
| Zdroj: | J Alzheimers Dis |
| ISSN: | 1875-8908 1387-2877 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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