Fries Gabriel R, Garza Steven De La, Zhao Ning O, Bass Andres W, Lima Camila N C, Kobori Nobuhide, Barichello Tatiana, Turecki Gustavo, Schulz Paul E, Diniz Breno S, Soares Jair C
Translational Psychiatry Program, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, 1941 East Rd, Houston, Texas, USA.
Neuroscience Graduate Program, The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, 6767 Bertner Ave, Houston, Texas, USA.
medRxiv. 2025 Apr 7:2025.04.06.25325186. doi: 10.1101/2025.04.06.25325186.
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.
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.
Amyloid beta (Aβ), Aβ, and total Tau levels were measured in plasma from individuals with BD and controls, and Aβ levels were measured in brains. EA and its acceleration (blood: GrimAge and DunedinPACE; brains: DNAmClock) 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 acceleration (DNAmClockAccel).
Individuals with BD showed an increase in Aβ (p=.049) and a decrease in the Aβ ratio (p=.035) compared to controls. A decrease in the Aβ ratio was also found in individuals with BD with high versus low AgeAccelGrim (p=.028). Brain Aβ levels significantly correlated with DNAmClockAccel (r=.270, p=.007), with those with high EA acceleration showing higher brain Aβ after controlling for confounders (p=.008).
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.
双相情感障碍（BD）与阿尔茨海默病（AD）风险升高有关。我们评估了BD患者的AD生物标志物，并测试了表观遗传衰老（EA）加速是否是驱动这些标志物变异性的潜在机制。
设计、地点、参与者：对59名BD在世个体和20名年龄及性别匹配的对照参与者进行横断面研究，并对46名BD个体的死后脑样本（布罗德曼区9/46）进行分析。
测量BD患者和对照者血浆中的淀粉样β蛋白（Aβ）、Aβ和总 Tau 水平，并测量脑中的Aβ水平。对所有样本估计EA及其加速情况（血液：GrimAge和DunedinPACE；大脑：DNAmClock）。如果BD患者在GrimAge加速（AgeAccelGrim）、DunedinPACE或DNAmClock加速（DNAmClockAccel）的第一或第四四分位数，则将其分为EA加速或减缓的四分位数。
与对照组相比，BD患者的Aβ升高（p = 0.049），Aβ比值降低（p = 0.035）。在AgeAccelGrim高与低的BD患者中也发现Aβ比值降低（p = 0.028）。脑Aβ水平与DNAmClockAccel显著相关（r = 0.270，p = 0.007），在控制混杂因素后，EA加速高的患者脑Aβ水平更高（p = 0.008）。
我们的结果提供了初步证据，表明EA可能解释BD患者AD风险的变异性，并可作为预防BD患者痴呆和AD的靶点。
