Additive Microglia-Mediated Neuronal Injury Caused by Amyloid-β and Bacterial TLR Agonists in Murine Neuron-Microglia Co-Cultures Quantified by an Automated Image Analysis using Cognition Network Technology

Abstract

Activated microglia is considered to be involved in the progression of Alzheimer's disease (AD). We investigated the effect of amyloid-β_1-40 (Aβ₄₀) and exogenous agonists of Toll-like receptor (TLR) 1/2 (Pam₃CSK₄) and TLR4 (LPS) on neurons in primary murine neuron-microglia co-cultures. Neuronal viability, assessed by quantifying the number of intact neuronal extensions and their crossings using a newly developed Definiens Cognition Network Technology-based method, was significantly decreased after treatment with Pam₃CSK₄, LPS, and Aβ₄₀. Combined treatment with Aβ₄₀ and Pam₃CSK₄ or LPS had an additive effect. Hence, in patients with AD, synergistic microglial activation by Aβ and bacterial products during infections might contribute to disease progression.