Dataset Information

A comparison of blood and brain-derived ageing and inflammation-related DNA methylation signatures and their association with microglial burdens.

ABSTRACT: Inflammation and ageing-related DNA methylation patterns in the blood have been linked to a variety of morbidities, including cognitive decline and neurodegenerative disease. However, it is unclear how these blood-based patterns relate to patterns within the brain and how each associates with central cellular profiles. In this study, we profiled DNA methylation in both the blood and in five post mortem brain regions (BA17, BA20/21, BA24, BA46 and hippocampus) in 14 individuals from the Lothian Birth Cohort 1936. Microglial burdens were additionally quantified in the same brain regions. DNA methylation signatures of five epigenetic ageing biomarkers ('epigenetic clocks'), and two inflammatory biomarkers (methylation proxies for C-reactive protein and interleukin-6) were compared across tissues and regions. Divergent associations between the inflammation and ageing signatures in the blood and brain were identified, depending on region assessed. Four out of the five assessed epigenetic age acceleration measures were found to be highest in the hippocampus (β range = 0.83-1.14, p ≤ 0.02). The inflammation-related DNA methylation signatures showed no clear variation across brain regions. Reactive microglial burdens were found to be highest in the hippocampus (β = 1.32, p = 5 × 10^-4 ); however, the only association identified between the blood- and brain-based methylation signatures and microglia was a significant positive association with acceleration of one epigenetic clock (termed DNAm PhenoAge) averaged over all five brain regions (β = 0.40, p = 0.002). This work highlights a potential vulnerability of the hippocampus to epigenetic ageing and provides preliminary evidence of a relationship between DNA methylation signatures in the brain and differences in microglial burdens.

SUBMITTER: Stevenson AJ

PROVIDER: S-EPMC9525452 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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A comparison of blood and brain-derived ageing and inflammation-related DNA methylation signatures and their association with microglial burdens.

Stevenson Anna J AJ McCartney Daniel L DL Gadd Danni A DA Shireby Gemma G Hillary Robert F RF King Declan D Tzioras Makis M Wrobel Nicola N McCafferty Sarah S Murphy Lee L McColl Barry W BW Redmond Paul P Taylor Adele M AM Harris Sarah E SE Russ Tom C TC McIntosh Andrew M AM Mill Jonathan J Smith Colin C Deary Ian J IJ Cox Simon R SR Marioni Riccardo E RE Spires-Jones Tara L TL

The European journal of neuroscience 20220406 9

Inflammation and ageing-related DNA methylation patterns in the blood have been linked to a variety of morbidities, including cognitive decline and neurodegenerative disease. However, it is unclear how these blood-based patterns relate to patterns within the brain and how each associates with central cellular profiles. In this study, we profiled DNA methylation in both the blood and in five post mortem brain regions (BA17, BA20/21, BA24, BA46 and hippocampus) in 14 individuals from the Lothian B ...[more]

PMID: 35362642

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Dataset Information

A comparison of blood and brain-derived ageing and inflammation-related DNA methylation signatures and their association with microglial burdens.

Publications

A comparison of blood and brain-derived ageing and inflammation-related DNA methylation signatures and their association with microglial burdens.

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