Impaired TGFβ Signaling in Plaque-Associated Microglia.

Biomolecules 2026

Krzyzan O, Kuhla A, Spittau B, Vidovic N

Abstract

Aging and Alzheimer’s disease (AD) 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 transforming growth factor β (TGF-β) signaling in the amyloid precursor protein and presenilin-1 (APP/PS1) transgenic mouse model of Alzheimer’s disease. Using confocal microscopy and 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 distribution in microglia, suggesting impaired canonical TGF-β 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.

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