In-vivo measurement of activated microglia in dementia

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Annachiara Cagnin, Hammersmith Hospital
  • ,
  • David J. Brooks
  • Angus M. Kennedy, Hammersmith Hospital
  • ,
  • Roger N. Gunn, Hammersmith Hospital
  • ,
  • R. Myers, Hammersmith Hospital
  • ,
  • Federico E. Turkheimer, Hammersmith Hospital
  • ,
  • Terry Jones, Hammersmith Hospital
  • ,
  • Richard B. Banati, Hammersmith Hospital, Department of Neuromorphology, Imperial College London, London, UK.

Background Activated microglia have a key role in the brain's immune response to neuronal degeneration. The transition of microglia from the normal resting state to the activated state is associated with an increased expression of receptors known as peripheral benzodiazepine binding sites, which are abundant on cells of mononuclear phagocyte lineage. We used brain imaging to study expression of these sites in healthy individuals and patients with Alzheimer's disease. Methods We studied 15 normal individuals (age 32-80 years), eight patients with Alzheimer's disease, and one patient with minimal cognitive impairment. Quantitative in-vivo measurements of glial activation were obtained with positron emission tomography (PET) and carbon-11-labelled (R)-PK11195, a specific ligand for the peripheral benzodiazepine binding site. Findings In normal individuals, regional [11C](R)-PK11195 binding did not significantly change with age, except in the thalamus, where an age-dependent increase was found. By contrast, patients with Alzheimer's disease showed significantly increased regional [11C](R)-PK11195 binding in the entorhinal, temporoparietal, and cingulate cortex. Interpretation In-vivo detection of increased [11C](R)-PK11195 binding in Alzheimer-type dementia, including mild and early forms, suggests that microglial activation is an early event in the pathogenesis of the disease.

Original languageEnglish
JournalLancet
Volume358
Issue9280
Pages (from-to)461-467
Number of pages7
ISSN0140-6736
DOIs
Publication statusPublished - 11 Aug 2001
Externally publishedYes

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