Neuroinflammation in healthy aging: A PET study using a novel Translocator Protein 18Â kDa (TSPO) radioligand, [18F]-FEPPA

One of the cellular markers of neuroinflammation is increased microglia activation, characterized by overexpression of mitochondrial 18 kDa Translocator Protein (TSPO). TSPO expression can be quantified in-vivo using the positron emission tomography (PET) radioligand [18F]-FEPPA. This study examined microglial activation as measured with [18F]-FEPPA PET across the adult lifespan in a group of healthy volunteers. We performed genotyping for the rs6971 TS.PO gene polymorphism to control for the known variability in binding affinity. Thirty-three healthy volunteers (age range: 19-82 years; 22 high affinity binders (HAB), 11 mixed affinity binders (MAB)) underwent [18F]-FEPPA PET scans, acquired on the High Resolution Research Tomograph (HRRT) and analyzed using a 2-tissue compartment model. Regression analyses were performed to examine the effect of age adjusting for genetic status on [18F]-FEPPA total distribution volumes (VT) in the hippocampus, temporal, and prefrontal cortex. We found no significant effect of age on [18F]-FEPPA VT (F (1,30) = 0.918; p = 0.346), and a significant effect of genetic polymorphism (F (1,30) = 8.767; p = 0.006). This is the first in-vivo study to evaluate age-related changes in TSPO binding, using the new generation TSPO radioligands. Increased neuroinflammation, as measured with [18F]-FEPPA PET was not associated with normal aging, suggesting that healthy elderly individuals may serve as useful benchmark against patients with neurodegenerative disorders where neuroinflammation may be present.