Acetylcholinesterase induces the expression of the β-amyloid precursor protein in glia and activates glial cells in culture

Abstract

Acetylcholinesterase (AChE) activities in CNS physiopathology are increasingly diverse and range from neuritogenesis, through synaptogenesis, to enhancement of amyloid fiber assembly. In Alzheimer's disease, senile plaques and neurodegeneration specially affect regions enriched for cholinergic synapses. In this study we show an effect of AChE that could contribute to the increased deposition of Aβ in certain regions. Affinity-purified AChE induced the expression of amyloid-β-precursor protein (β-APP) in glial cells in a concentration-dependent manner up to 5 nM. In glia, AChE also increased inducible nitric oxide synthase (iNOS) assessed by immunocytochemistry and decreased reductive metabolism as evidence of cell activation. AChE could increase the expression of β-APP in astrocytes and microglia as result of the activation of glial cells. As a whole, we found that AChE has additional effects that could result in an increased synthesis of Aβ, both by increasing β-APP expression of astrocytes and by further activating glial cells.

Keywords

• Acetylcholinesterase
• AChE inhibitors
• β-APP
• Alzheimer's disease
• iNOS
• Glia