In vivo evidence for microglial activation in neurodegenerative dementia

A. Cagnin, M. Kassiou, S. R. Meikle, R. B. Banati

Research output: Contribution to journalArticlepeer-review

Abstract

Evidence from numerous neuropathological observations and in vivo clinical imaging studies suggests a prominent role of activated microglia, the main effector cell of the brain's innate immune system, in Alzheimer's disease and other neurodegenerative diseases. Though the comprehensive molecular definition of the microglial activation process is still incomplete, the de novo expression of 'peripheral benzodiazepine-binding sites (PBBS)' by activated but not resting microglia has been established as a useful descriptor of functional state changes in microglia. As microglial transformation to an activated state is closely linked to progressive changes in brain disease, the detection of activated microglia can provide information about disease distribution and rate of disease progression. Positron emission tomography (PET) and [ 11C](R)-PK11195, a specific ligand of the PBBS, have been used to study systematically microglial activation in vivo. Significant microglial activation is present in the brains of patients with neurodegenerative dementia even at early and possibly preclinical stages of the disease with a spatial distribution reflecting different clinical phenotypes. We review some of the posited functions of activated microglia in the pathophysiology of dementia and speculate on the relationship between increased regional [11C](R)- PK11195 signals and the ensuing changes in brain volume. Finally, we provide a brief outlook on the development of new radioligands for the PBBS.

Original languageEnglish
Pages (from-to)107-114
Number of pages8
JournalActa Neurologica Scandinavica
Volume114
Issue numberSUPPL. 185
DOIs
Publication statusPublished - Aug 2006

Keywords

  • Alzheimer's disease
  • Microglia
  • Neurodegenerative diseases
  • Neuroinflammation
  • PK11195
  • Positron emission tomography

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

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