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

Abstract

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.

N-3 polyunsaturated fatty acids in animal models with neuroinflammation: An update

“…As reported above, these bioactive lipid mediators are sufficient to reduce neuroinflammation in stroke, i.c.v. LPS, neuropathic pain models, and surgery-induced (Suridjan et al, 2015). Since n-3 PUFA modulate microglia markers such as Iba-1 as described above, future clinical studies in humans could image neuroinflammation following n-3 PUFA treatment and relate TSPO binding with the reduction with symptoms.…”

Imaging Translocator Protein as a Biomarker of Neuroinflammation in Dementia

“…Autoradiography studies demonstrated greater binding of 3 H-DAA1106 to TSPO in both a transgenic AD mouse model (Maeda et al, 2011) and in human tissue from AD brains (Gulyas et al, 2009). In addition, binding with 18 F-FEPPA was shown to be greater in AD patients than in controls in hippocampus and white matter regions such as internal capsule and cingulum bundle, as well as in prefrontal, temporal, parietal, and occipital cortices (Suridjan et al, 2015). Greater 18 F-FEPPA binding also correlated with worse performance on some cognitive measures (Suridjan et al, 2015).…”

“…In addition, binding with 18 F-FEPPA was shown to be greater in AD patients than in controls in hippocampus and white matter regions such as internal capsule and cingulum bundle, as well as in prefrontal, temporal, parietal, and occipital cortices (Suridjan et al, 2015). Greater 18 F-FEPPA binding also correlated with worse performance on some cognitive measures (Suridjan et al, 2015). Finally, in studies using 11 C-( R )-PK-11195 and 11 C-PBR28, TSPO binding was found to increase with progression of AD (Fan, Okello, Brooks, & Edison, 2015; Kreisl et al, 2016).…”

Microglial positron emission tomography (PET) imaging in epilepsy: Applications, opportunities and pitfalls

“…Human studies using these secondgeneration ligands have demonstrated increased TSPO expression in a variety of CNS disorders, including Alzheimer's disease [37], amyotrophic lateral sclerosis [34], and multiple sclerosis [38].…”