Neuroinflammation and cognitive decline: a TSPO‐PET imaging study.

Abstract

AbstractBackgroundNeuroinflammation is a key driving factor of the pathophysiology of neurodegenerative diseases, including Alzheimer’s disease (AD). Microglia, a major immune cell of the central nervous system, may exert protective effects in the early stages of AD, while may damage the brain milieu in later stages of the disease continuum. The microglial response is mirrored by an increase in the detection of translocator protein (TSPO), a mitochondrial membrane protein that can be targeted with positron emission tomography (PET) imaging. Here, we aim to assess the impact of neuroinflammation on cognition across the AD continuum.Method48 participants (23 patients with AD, 14 patients with mild cognitive impairment (MCI), and 11 cognitively normal controls (CN)) underwent TSPO‐PET (flutriciclamide, [18F]GE180) imaging, magnetic resonance imaging (MRI), and neuropsychological testing. All participants were either high‐ or mixed‐affinity binders for TSPO‐PET tracers, as revealed by TSPO genotyping. The spectral analysis generated a flutriciclamide impulse response function at 90 minutes (IRF90) image, which reflects its volume of distribution. Region of interest and voxel‐wise analyses were conducted to explore the relationship between IRF90 and neuropsychological assessment performance on a group‐level.ResultTSPO‐PET binding was significantly higher in patients with AD compared to CNs across the whole brain, while patients with MCI demonstrated greater TSPO‐PET binding in the hippocampus and medial temporal lobe, compared to CNs. Significant negative associations were observed between neuropsychological assessment scores and IRF90, particularly in the temporal lobe (table 1). At a voxel level, negative correlations were seen between mini‐mental state examination score and IRF90 in temporoparietal regions (figure 1).ConclusionMicroglial response, a marker of neuroinflammation, is elevated in patients with AD and MCI, as measured using TSPO‐PET (flutriciclamide, [18F]GE180) imaging. Heightened neuroinflammation, measured by TSPO‐PET, may exert damaging effects on the brain, as highlighted here by the negative association between TSPO‐PET binding and neuropsychometric assessment performance. This study emphasises the requirement to improve our understanding of the role of neuroinflammation in AD in order to identify pharmacological targets in the future.