10 research outputs found
Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume
- Author
- Adeli A.
- Agostino D.D.
- Aisen P.
- Albers C.S.
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- Publication venue
- Springer Nature
- Publication date
- 01/01/2022
- Field of study
Get PDFThe concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimerâs Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-ÎČ PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimerâs Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-ÎČ positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimerâs disease-related phenotypes, including measures of cognition or brain Amyloid-ÎČ burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes
New insights into the genetic etiology of Alzheimer's disease and related dementias
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