title: 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-1b (IL-1b)-, 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 histocampatibility complex class II cell surface receptors, encoded by the human leukocyte antigen DP-DQ-DR, were detected in the cortex and hippocampus. IL-1b 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.
authors.affiliation: Department of Clinical Neurosciences, Brain Repair Centre, University of Cambridge, Cambridge, UK. bellucci@med.unibs.it
authors.forename: Arianna
authors.initials: A
authors.lastname: Bellucci
authors.forename: Orso
authors.initials: O
authors.lastname: Bugiani
authors.forename: Bernardino
authors.initials: B
authors.lastname: Ghetti
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Spillantini
mesh_terms: D000328:Adult; D017668:Age of Onset; D051546:Cyclooxygenase 2 / Q000378:metabolism; D057180:Frontotemporal Dementia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism*; D053583:Interleukin-1beta; D017628:Microglia / Q000473:pathology*; D008875:Middle Aged; D009154:Mutation; D016875:tau Proteins / Q000235:genetics*
chemical_list: D018836:Inflammation Mediators; D053583:Interleukin-1beta; C054369:MAPT protein, human; D016875:tau Proteins; D051546:Cyclooxygenase 2