Association between epigenetic aging acceleration and amyloid biomarkers in bipolar disorder
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Objectives
Bipolar disorder (BD) has been associated with an elevated risk of Alzheimer’s Disease (AD). We assessed AD biomarkers in BD and tested whether epigenetic aging (EA) acceleration is a potential mechanism driving variability in these markers.
Design, Setting, Participants
Cross-sectional study of n=59 living individuals with BD and n=20 age- and sex-equated control participants, as well as analyses of postmortem brain samples (Brodmann area 9/46) from n=46 individuals with BD.
Measurements
Amyloid beta (Aβ) 40 , Aβ 42 , and total Tau levels were measured in plasma from individuals with BD and controls, and Aβ 42 levels were measured in brains. EA and its acceleration (blood: GrimAge and DunedinPACE; brains: DNAmClock Cortical ) were estimated for all samples. Individuals with BD were split into quartiles with accelerated or slower EA if they were in the first or fourth quartiles for GrimAge acceleration (AgeAccelGrim), DunedinPACE, or DNAmClock Cortical acceleration (DNAmClock Cortical Accel).
Results
Individuals with BD showed an increase in Aβ 40 (p=.049) and a decrease in the Aβ 42/40 ratio (p=.035) compared to controls. A decrease in the Aβ 42/40 ratio was also found in individuals with BD with high versus low AgeAccelGrim (p=.028). Brain Aβ 42 levels significantly correlated with DNAmClock Cortical Accel (r 2 =.270, p=.007), with those with high EA acceleration showing higher brain Aβ 42 after controlling for confounders (p=.008).
Conclusions
Our results provide preliminary evidence that EA may explain the variability in AD risk in individuals with BD and could act as a target for preventing dementia and AD in BD.
