Telomere Shortening in the Alzheimer's Disease Neuroimaging Initiative Cohort.
J Alzheimers Dis
; 71(1): 33-43, 2019.
Article
em En
| MEDLINE
| ID: mdl-31322561
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 (Nâ=â1918 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)â=â-0.23) and male sex (ESâ=â-0.26). Neither baseline T/S ratio (ESâ=â-0.036) nor T/S ratio change (ESâ=â0.046) differed significantly between AD diagnostic groups. MCI/AD converters showed greater, but non-significant, telomere shortening compared to non-converters (ESâ=â-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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Alzheimer
/
Neuroimagem
/
Encurtamento do Telômero
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Aged
/
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article