Microglial activation and amyloid deposition in mild cognitive impairment: a PET study

Neurology. 2009 Jan 6;72(1):56-62. doi: 10.1212/01.wnl.0000338622.27876.0d.


Background: Activated microglia may play a role in the pathogenesis of Alzheimer disease (AD) as they cluster around beta-amyloid (Abeta) plaques. They are, therefore, a potential therapeutic target in both AD and its prodrome amnestic mild cognitive impairment (MCI).

Objective: To characterize in vivo with (11)C-(R)-PK11195 and (11)C-PIB PET the distribution of microglial activation and amyloid deposition in patients with amnestic MCI.

Methods: Fourteen subjects with MCI had (11)C-(R)-PK11195 and (11)C-PIB PET with psychometric tests.

Results: Seven out of 14 (50%) patients with MCI had increased cortical (11)C-PIB retention (p < 0.001) while 5 out of 13 (38%) subjects with MCI showed increased (11)C-(R)-PK11195 uptake. The MCI subgroup with increased (11)C-PIB retention also showed increased cortical (11)C-(R)-PK11195 binding (p < 0.036) though this increase only remained significant in frontal cortex after a correction for multiple comparisons. There was no correlation between regional levels of (11)C-(R)-PK11195 and (11)C-PIB binding in individual patients with MCI: only three of the five MCI cases with increased (11)C-(R)-PK11195 binding had increased levels of (11)C-PIB retention.

Conclusions: Our findings indicate that, while amyloid deposition and microglial activation can be detected in vivo in around 50% of patients with mild cognitive impairment (MCI), these pathologies can occur independently. The detection of microglial activation in patients with MCI suggests that anti-inflammatory therapies may be relevant to the prevention of AD.

MeSH terms

  • Aged
  • Alzheimer Disease / complications
  • Amyloid beta-Peptides / metabolism*
  • Aniline Compounds
  • Benzothiazoles / metabolism
  • Brain Mapping
  • Carbon Radioisotopes / metabolism
  • Cognition Disorders / diagnosis
  • Cognition Disorders / diagnostic imaging*
  • Cognition Disorders / etiology
  • Cognition Disorders / pathology*
  • Female
  • Follow-Up Studies
  • Humans
  • Isoquinolines / metabolism
  • Magnetic Resonance Imaging
  • Male
  • Microglia / diagnostic imaging*
  • Microglia / metabolism
  • Microglia / pathology
  • Middle Aged
  • Neuropsychological Tests
  • Positron-Emission Tomography*
  • Thiazoles


  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
  • Amyloid beta-Peptides
  • Aniline Compounds
  • Benzothiazoles
  • Carbon Radioisotopes
  • Isoquinolines
  • Thiazoles
  • PK 11195