Presence of Reactive Microglia and Neuroinflammatory Mediators in a Case of Frontotemporal Dementia with P301S Mutation.

Abstract

Background: Recent findings, showing the presence of an inflammatory process in the brain of transgenic mice expressing P301S mutated human tau protein, indicate that neuroinflammation may contribute to tau-related degeneration in frontotemporal dementia and parkinsonism linked to chromosome 17 with tau mutations (FTDP-17T). Objective: To investigate the occurrence of neuroinflammatory changes in the brain of a patient affected by FTDP-17T associated with the P301S mutation and showing a frontotemporal dementia phenotype as well as in the brain of a patient affected by another FTDP-17T phenotype: multiple system tauopathy with presenile dementia. Methods: We used immunohistochemical methods to visualize activated microglia, interleukin-1 beta (IL-1 beta)-, cyclooxygenase-2 (COX-2)-expressing cells. Results: In the brain of the patient with the P301S mutation, a strong neuroinflammatory reaction was present. Activated microglia/infiltrating macrophages expressing the cluster of differentiation 68 and major histo-campatibility complex class II cell surface receptors, encoded by the human leukocyte antigen DP-DQ-DR, were detected in the cortex and hippocampus. IL-1 beta and COX-2 expression were induced in neuronal and glial cells. These neuroinflammatory changes were different from those observed in the brain of the patient bearing the +3 mutation, where macrophage infiltration was absent, microglial cells displayed an earlier stage of activation and COX-2 was not detected. Conclusions: Our findings suggest that microglial activation and the production of proinflammatory mediators by phospho-tau-positive neurons and glial cells may differentially contribute to neuronal death and disease progression in neurodegenerative tauopathies