Brain inflammation accompanies amyloid in the majority of mild cognitive impairment cases due to Alzheimer’s disease

Abstract

Subjects with mild cognitive impairment associated with cortical amyloid-β have a greatly increased risk of progressing to Alzheimer's disease. We hypothesized that neuroinflammation occurs early in Alzheimer's disease and would be present in most amyloid-positive mild cognitive impairment cases. ¹¹C-Pittsburgh compound B and ¹¹C-(R)-PK11195 positron emission tomography was used to determine the amyloid load and detect the extent of neuroinflammation (microglial activation) in 42 mild cognitive impairment cases. Twelve age-matched healthy control subjects had ¹¹C-Pittsburgh compound B and 10 healthy control subjects had ¹¹C-(R)-PK11195 positron emission tomography for comparison. Amyloid-positivity was defined as ¹¹C-Pittsburgh compound B target-to-cerebellar ratio above 1.5 within a composite cortical volume of interest. Supervised cluster analysis was used to generate parametric maps of ¹¹C-(R)-PK11195 binding potential. Levels of ¹¹C-(R)-PK11195 binding potential were measured in a selection of cortical volumes of interest and at a voxel level. Twenty-six (62%) of 42 mild cognitive impairment cases showed a raised cortical amyloid load compared to healthy controls. Twenty-two (85%) of the 26 amyloid-positive mild cognitive impairment cases showed clusters of increased cortical microglial activation accompanying the amyloid. There was a positive correlation between levels of amyloid load and ¹¹C-(R)-PK11195 binding potentials at a voxel level within subregions of frontal, parietal and temporal cortices. ¹¹C-(R)-PK11195 positron emission tomography reveals increased inflammation in a majority of amyloid positive mild cognitive impairment cases, its cortical distribution overlapping that of amyloid deposition.

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