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

Subjects with mild cognitive impairment associated with cortical amyloid-beta 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. C-11-Pittsburgh compound B and C-11-(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 C-11-Pittsburgh compound B and 10 healthy control subjects had C-11-(R)-PK11195 positron emission tomography for comparison. Amyloid-positivity was defined as C-11-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 C-11-(R)-PK11195 binding potential. Levels of C-11-(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 C-11-(R)-PK11195 binding potentials at a voxel level within subregions of frontal, parietal and temporal cortices. C-11-(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.