Fig. 6

Schematic diagram of our working model for the glymphatic system mediated Aβ and apoE clearance and microglia mediated Aβ degradation synergistically preventing Aβ plague formation in the early stages of the AD mouse model. 3-month-old APP/PS1 mice show extracellular and intraneuronal accumulation of Aβ because of the long-term of expression transgenic APP/PS1. Excessive interstitial Aβ may result in activation of astrocytes with loss of perivascular AQP4 polarization, subsequently impairing glymphatic clearance of Aβ and apoE. On the other hand, microglia undergo activation and promote Aβ clearance, potentially preventing Aβ plaque formation. AQP4 deletion exacerbates glymphatic transport impairment and intraneuronal accumulation of Aβ and apoE, but Aβ plaques have not yet aggregated, which may be related to the increase of phagocytosis of reactive microglia