Preliminary Investigation of the Association Between Epigenetic Aging Acceleration and Amyloid Biomarkers in Bipolar Disorder.

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 associated with changes in these markers. DESIGN, SETTING, PARTICIPANTS: Cross-sectional study of n = 58 living individuals with BD and n = 20 age- and sex-matched 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 slower or accelerated 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 a decrease in the Aβ(42/40) ratio (p = 0.048) compared to controls, and a significant decrease in the Aβ(42/40) ratio was also found in individuals with BD with high versus low AgeAccelGrim (p = 0.048). Brain Aβ(42) levels significantly correlated with DNAmClock(Cortical)Accel (r(2) = 0.270, p = 0.007), with those with high EA acceleration showing higher brain Aβ(42) after controlling for confounders (p = 0.008). CONCLUSIONS: Our results provide preliminary evidence that accelerated EA is associated with markers of AD in individuals with BD, suggesting it as a potential target in efforts to prevent dementia and AD in BD.