Characterization of microglial response in the female 3xTgAD Model

Abstract

Alzheimer's disease (AD) involves severe impairment of cognitive and executive functions and represents 60-70% of all cases of dementia. Neuropathologically, it is characterized by the deposition of beta-amyloid peptide in extracellular neuritic plaques and the formation of intraneuronal neurofibrillary tangles, which elimination has been the unsuccessful goal of different therapies. However, little is known about the progressing neuroinflammatory process, characterized by an increase in the number and morphological changes of microglial cells at different stages of the disease. The aim of this study is to characterize the morphological differences of microglial cells in the hippocampus of an aged murine model of Alzheimer's disease to elucidate whether, associated with age and tau and beta amyloid deposits, there is an active proinflammatory phenotype different from the physiological pattern and how it is related to the formation of tau neurofibrillary tangles. Twelve female mice (healthy controls and 3xTgAD, n = 6 per group) between 19 and 22 months were used and 10 cells from each animal were randomly analysed using the AnalyzeSkeleton and FracLac extensions of the Image-J program. No significant differences were found between both groups. Secondly, we studied microglial relationship with tau accumulation in controls and 3xTgAD animals at different stages (9, 12 and 15 months, n=3). Our results show an increase in both the number of microglia cells and intracellular tau tangles associated with age, as well as a strong relationship between both variables. In sum, we must consider the age variable to understand the rol of microglial cells in AD neurodegeneration process. Understanding their morphological heterogeneity may be one of the keys of this neurodegenerative disorder.