Imaging Translocator Protein as a Biomarker of Neuroinflammation in Dementia

Neuroinflammation has long been considered a potential contributor to neurodegenerative disorders that result in dementia. Accumulation of abnormal protein aggregates in Alzheimer's disease, frontotemporal dementia, and dementia with Lewy bodies is associated with the activation of microglia and astrocytes into proinflammatory states, and chronic low-level activation of glial cells likely contributes to the pathological changes observed in these and other neurodegenerative diseases. The 18kDa translocator protein (TSPO) is a key biomarker for measuring inflammation in the brain via positron emission tomography (PET). Increased TSPO density has been observed in brain tissue from patients with neurodegenerative diseases and colocalizes to activated microglia and reactive astrocytes. Several radioligands have been developed to measure TSPO density in vivo with PET, and these have been used in clinical studies of different dementia syndromes. However, TSPO radioligands have limitations, including low specific-to-nonspecific signal and differential affinity to a polymorphism on the TSPO gene, which must be taken into consideration in designing and interpreting human PET studies. Nonetheless, most PET studies have shown that increased TSPO binding is associated with various dementias, suggesting that TSPO has potential as a biomarker to further explore the role of neuroinflammation in dementia pathogenesis and may prove useful in monitoring disease progression.