Presence of reactive microglia and neuroinflammatory mediators in a case of frontotemporal dementia with P301S mutation

Arianna Bellucci, Orso Bugiani, Bernardino Ghetti, Maria Grazia Spillantini

Research output: Contribution to journalArticle

34 Scopus citations


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-1β (IL-1β)-, 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-1β 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.

Original languageEnglish (US)
Pages (from-to)221-229
Number of pages9
JournalNeurodegenerative Diseases
Issue number4
StatePublished - May 1 2011



  • Cyclooxygenase 2
  • Frontotemporal dementia and parkinsonism linked to chromosome 17 with tau mutations
  • Interleukin 1β
  • Microglia
  • Neuroinflammation

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

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