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

Activated microglia is considered to be involved in the progression of Alzheimer's disease (AD). We investigated the effect of amyloid-beta(1-40) (A beta(40)) and exogenous agonists of Toll-like receptor (TLR) 1/2 (Pam(3)CSK(4)) 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 Pam(3)CSK(4), LPS, and A beta(40). Combined treatment with A beta(40) and Pam(3)CSK(4) or LPS had an additive effect. Hence, in patients with AD, synergistic microglial activation by A beta and bacterial products during infections might contribute to disease progression.