In-vivo imaging of grey and white matter neuroinflammation in Alzheimer's disease: a positron emission tomography study with a novel radioligand, [18F]-FEPPA.

Our primary aim was to compare neuroinflammation in cognitively intact control subjects and patients with Alzheimer's disease (AD) by using positron emission tomography (PET) with translocator protein 18 kDa (TSPO)-specific radioligand [(18)F]-FEPPA. [(18)F]-FEPPA PET scans were acquired on a high-resolution research tomograph in 21 patients with AD (47- 81 years) and 21 control subjects (49-82 years). They were analyzed by using a 2-tissue compartment model with arterial plasma input function. Differences in neuroinflammation, indexed as [(18)F]-FEPPA binding were compared, adjusting for differences in binding affinity class as determined by a single polymorphism in the TSPO gene (rs6971). In grey matter areas, [(18)F]-FEPPA was significantly higher in AD compared with healthy control subjects. Large increases were seen in the hippocampus, prefrontal, temporal, parietal and occipital cortex (average Cohen's d= 0.89). Voxel-based analyses confirmed significant clusters of neuroinflammation in the frontal, temporal and parietal cortex in patients with AD. In white matter, [(18)F]-FEPPA binding was elevated in the posterior limb of the internal capsule, and the cingulum bundle. Higher neuroinflammation in the parietal cortex (r= -0.7, P= 0.005), and posterior limb of the internal capsule (r= -0.8, P=0.001) was associated with poorer visuospatial function. In addition, a higher [(18)F]-FEPPA binding in the posterior limb of the internal capsule was associated with a greater impairment in language ability (r= -0.7, P=0.004). Elevated neuroinflammation can be detected in AD patients throughout the brain grey and white matter by using [(18)F]-FEPPA PET. Our results also suggest that neuroinflammation is associated with some cognitive deficits.