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

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

A Okello  1 , P Edison, H A Archer, F E Turkheimer, J Kennedy, R Bullock, Z Walker, A Kennedy, N Fox, M Rossor, D J Brooks
Affiliations

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

A Okello et al. Neurology. .

Abstract

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.

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Figures

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Figure 1 Scatterplot showing 11C-(R)-PK11195 binding potentials in frontal cortex of controls, and mild cognitive impairment (MCI) subgroups; PIB-positive (+ve) and PIB-negative (−ve) MCI The dotted horizontal line shows controls' mean + 2 SD.
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Figure 2 11C-(R)-PK11195 binding potentials and corresponding PIB ratio images in two patients with PIB-positive mild cognitive impairment (MCI) MCI-I has normal PK binding and MCI-II has increased PK binding.
See this image and copyright information in PMC

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