# Impaired TGFβ Signaling in Plaque-Associated Microglia

## TL;DR

The study finds that microglia in Alzheimer's disease mouse models have abnormal shapes and disrupted TGFβ signaling, which may contribute to the disease's progression.

## Contribution

This work reveals impaired TGFβ signaling in plaque-associated microglia in an Alzheimer's disease mouse model.

## Key findings

- APP/PS1 mice show disturbed glial morphology compared to wild-type mice.
- Altered pSMAD2 distribution suggests impaired canonical TGF-β signaling in microglia.
- Dysfunctional TGF-β signaling may play a role in Alzheimer’s disease pathogenesis.

## 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.