Impaired TGFβ Signaling in Plaque-Associated Microglia

Aging and Alzheimer’s disease are associated with profound changes in glial cell morphology and signaling. This study investigates the three-dimensional morphology of microglia and the intracellular localization of phosphorylated SMAD proteins as downstream effectors of TGF-β signaling in the APP/PS1 transgenic mouse model of Alzheimer’s disease. Using confocal microscopy and the Simple Neurite Tracer software, we reconstructed and quantitatively analyzed glial cell morphology in aged wild-type and APP/PS1 mice. Immunofluorescence staining revealed altered pSMAD2 and pSMAD1/5/8 distribution in microglia, suggesting impaired canonical TGF-β and BMP signaling. Our findings indicate a disturbed glial morphology and dysfunctional TGF-β signaling cascade in the APP/PS1 model, underlining their potential role in Alzheimer’s disease pathogenesis.