Alterations in diacylglycerol kinase θ define early pathological features of Alzheimer's disease in a mouse model

Background Diacylglycerol kinase theta (DGKθ) is an enzyme involved in lipid signaling pathways and has been implicated in Alzheimer's disease (AD). DGKθ plays a crucial role in regulating diacylglycerol and phosphatidic acid levels, which are important for neuronal function and survival. Dysregulation of DGKθ leads to abnormal lipid signaling, contributing to neuroinflammation, synaptic dysfunction, and neurodegeneration—hallmarks of AD. Objective This study aimed to assess the involvement of DGKθ in AD by measuring DGKθ levels as a function of age in the brains of APP/PS1 mice and associating its changes with key AD neuropathological markers. Methods To investigate the role of DGK-θ in AD, brain tissues from young and aged APP/PS1 transgenic and wild-type mice were analyzed using western blot, immunohistochemistry, and Pearson correlation analyses to establish relationships between protein expression levels. Results We found that DGKθ levels were higher in older, but not in younger, APP/PS1 mice compared to age-matched controls. Notably, there was a positive correlation between DGKθ levels, Aβ 42 levels, and astrogliosis. Conclusions These results suggest that DGKθ may play an important role in AD and that its modulation could represent a potential therapeutic strategy for this insidious disorder.