Microglial activation and amyloid deposition in mild cognitive impairment

Abstract

Background: Activated microglia may play a role in the pathogenesis of Alzheimer disease (AD) as they cluster around beta-amyloid (Aβ) 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 ¹¹C-(R)-PK11195 and ¹¹C-PIB PET the distribution of microglial activation and amyloid deposition in patients with amnestic MCI. Methods: Fourteen subjects with MCI had ¹¹C-(R)-PK11195 and ¹¹C-PIB PET with psychometric tests. Results: Seven out of 14 (50%) patients with MCI had increased cortical ¹¹C-PIB retention (p < 0.001) while 5 out of 13 (38%) subjects with MCI showed increased ¹¹C-(R)-PK11195 uptake. The MCI subgroup with increased ¹¹C-PIB retention also showed increased cortical ¹¹C-(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 ¹¹C-(R)-PK11195 and ¹¹C-PIB binding in individual patients with MCI: only three of the five MCI cases with increased ¹¹C-(R)-PK11195 binding had increased levels of ¹¹C-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.