Increased radioligand binding to translocator protein correlates with worsened clinical severity and atrophy in Alzheimer's disease

Abstract

We previously demonstrated that radioligand binding to the 18 kDa translocator protein (TSPO), a marker for inflammation, was greater in patients with Alzheimer's disease (AD) than controls and correlated with clinical severity. We sought to determine the relationship between TSPO binding and progression of AD in a longitudinal study. Eleven patients with either AD or mild cognitive impairment and 8 age-matched controls underwent TSPO PET imaging with 11C-PBR28 at baseline and again after median follow up of 2.7 years. MRI, Pittsburgh Compound B (PIB) PET, and cognitive testing were also performed at baseline and follow up. PET images were corrected for partial volume effects. Regional 11C-PBR28 standardized uptake value ratios were determined using cerebellum as pseudo-reference region. PIB distribution volume ratios were determined using Logan graphical method with cerebellar reference. Among patients, there was a significant correlation between increase in 11C-PBR28 binding and a decline in raw scores on Block Design, Trail Making part B, and Boston Naming Test. The strongest of such correlations occurred in prefrontal and parietal cortices (R > 0.68, P < 0.03). Percent change in 11C-PBR28 binding negatively correlated with %change in voxel count in prefrontal, parietal, and temporal cortices (R < -0.52, P < 0.03). Percent change in 11C-PBR28 correlated with %change in PIB binding in occipital cortex only (R = 0.63, P = 0.037). Controls showed no correlation between 11C-PBR28 binding and brain atrophy. Among patients, ApoE4 carriers (n = 7) had greater increase in 11C-PBR28 binding than non-carriers (n = 4) in inferior temporal cortex (P = 0.042, Mann-Whitney U Test). TSPO increases with worsening clinical severity and cortical atrophy in AD. Larger studies are needed to better determine the relationship between TSPO, fibrillary amyloid load, and ApoE genotype. 11C-PBR28 PET has promise for monitoring AD progression.