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 18kDa (TSPO)-specific radioligand [F-18]-FEPPA. [F-18]-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 [F-18]-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, [F-18]-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, [F-18]-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 [F-18]-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 [F-18]-FEPPA PET. Our results also suggest that neuroinflammation is associated with some cognitive deficits.