Molecular imaging of neuroinflammation in Alzheimer's disease and mild cognitive impairment

Neuroinflammatory changes have been demonstrated to be an important feature of Alzheimer's disease (AD); however, the exact role of neuroinflammation and its progression during disease is still not well understood. One of the main drivers of the neuroinflammatory process are microglial cells. Positron Emission Tomography allows for the quantification of microglial activation by labelling the Translocator Protein 18 kDa (TSPO), which becomes overexpressed upon activation of microglial cells. Several radioligands have been designed to target TSPO and have been studied in-vivo in AD populations. While most studies have shown important increases in TSPO binding in AD populations compared to healthy volunteers, whether the neuroinflammatory progress occurs early on or later during disease is still unclear. In order to investigate the early changes in neuroinflammation, studies have sought to investigate microglial activation in patients with mild cognitive impairment (MCI), which is defined as a transitional stage between normal aging and dementia. In this prodromal population, conflicting results have been reported with some studies reporting increased binding in MCI, while others demonstrate no differences from controls. Here we review the TSPO PET studies in AD and MCI populations and discuss the important methodological considerations of imaging microglial activation.