Microglial Aβ clearance and Alzheimer's disease

Abstract

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases responsible for progressive dementia. Accumulation of activated microglia in and around senile plaques has been demonstrated in autopsied brains from AD patients, and considered to modulate amyloid β (Aβ) clearance, inflammation and oxidative stress. Our research suggested that activated microglia in the advanced stage of AD model mice showed higher expression levels of CD14/TLR. CD14/TLR4 complex is known to play vital role in immune response, and we showed that the complex is needed for microglial Aβ clearance. We also demonstrated therapeutic effects of galantamine using AD model mice. Galantamine is one of the cholinesterase inhibitors already used in clinical application. Galantamine is also known as an allosterically potentiating ligand of nicotinic acetylcholine receptor (nAChR). Stimulation of microglial α7 nAChR results in anti–inflammation and Aβ clearance. We showed α7 nAChR was expressed in early stage of activated microglia and earlier treatment of galantamine enhanced Aβ clearance.