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The presence of activated microglia in the brains of healthy elderly people is a matter of debate. We aimed to clarify the degree of microglial activation in aging and dementia as revealed by different tracers by comparing the binding potential (BP ND ) in various brain regions using a first-generation translocator protein (TSPO) tracer [ 11 C]( R)PK11195 and a second-generation tracer [ 11 C]DPA713. The BP ND levels, estimated using simplified reference tissue models, were compared among healthy young and elderly individuals and patients with Alzheimer's disease (AD) and were correlated with clinical scores. An analysis of variance showed category-dependent elevation in levels of [ 11 C]DPA713 BP ND in all brain regions and showed a significant increase in the AD group, whereas no significant changes among groups were found when [ 11 C]( R)PK11195 BP ND was used. Cognito-mnemonic scores were significantly correlated with [ 11 C]DPA713 BP ND levels in many brain regions, whereas [ 11 C]( R)PK11195 BP ND failed to correlate with the scores. As mentioned elsewhere, the present results confirmed that the second-generation TSPO tracer [ 11 C]DPA713 has a greater sensitivity to TSPO in both aging and neuronal degeneration than [ 11 C]( R)PK11195. Positron emission tomography with [ 11 C]DPA713 is suitable for the delineation of in vivo microglial activation occurring globally over the cerebral cortex irrespective of aging and degeneration.

Background: The neuroinflammatory glial response contributes to the degenerative process in Parkinson's disease (PD). However, the pattern of microglial progression remains unclear., Methods: We evaluated microglial activation in early stage PD patients by quantifying changes in neuroinflammation using PET with [(11)C]DPA713, a selective PET tracer for microglial activation. Eleven PD patients (Hoehn and Yahr stages 1-2) without dementia underwent the [(11)C]DPA713 PET scan two times with 1 year apart. The binding potential (BPND) was estimated with the simplified reference tissue model. Voxelwise and regions of interest analyses were used to compare the regional BPND among groups., Results: Significant increase in [(11)C]DPA713 BPND was found extrastriatally in the occipital, temporal and parietal cortex in PD patients, and the degree of BPND became much higher over the brain regions predominantly in the temporal and occipital cortex 1 year later., Conclusion: The current results indicated that an extrastriatal spreading of microglial activation reflects one of PD pathophysiology occurring at an early stage.

Introduction Chronic activation of microglia accelerates the neurodegenerative process in multiple sclerosis (MS). Although disease modifying therapy (DMT) is reportedly effective for neuroinflammatory responses in MS, the progression of neuroinflammation after DMT remains unclear. Methods We evaluated microglial activation in six clinically stable relapsing-remitting MS patients after DMT by quantifying changes in translocator protein (TSPO) density using PET with [ 11 C ]DPA713, a selective TSPO tracer for microglial activation. All patients underwent [ 11 C ]DPA713 PET scans twice, and the scans were conducted one year apart. The binding potential (BP ND ) of the tracer was estimated using a simplified reference tissue model. Results [ 11 C ]DPA713 BP ND measured at 6 months after DMT was significantly higher in the MS group than that in the control group. Compared with the first PET measurement, the one-year PET measurement revealed significantly elevated [ 11 C ]DPA713 BP ND in broader brain regions covering the temporal and parietal cortices after one year of DMT. Conclusions The current results indicate that microglial activation may proceed in the entire brain of clinically stable MS patients even after receiving DMT. [ABSTRACT FROM AUTHOR]

• Widespread TSPO PET signal increases in cortical grey matter in AD and other neurodegenerative disorder. • Cortico-limbic signal increases in AD, MCI , other neurodegenerative disorders, mood disorders, and MS. • Thalamic signal increases in AD, other neurodegenerative disorders, MS, and chronic pain and functional disorders. • Quantification method (V T vs. reference tissue models) accounted for 25% of transdiagnostic between-study variability. • Patient age and radioligand generation accounted for 9 and 5% of transdiagnostic between-study variability. The 18-kDa translocator protein (TSPO) is increasingly recognized as a molecular target for PET imaging of inflammatory responses in various central nervous system (CNS) disorders. However, the reported sensitivity and specificity of TSPO PET to identify brain inflammatory processes appears to vary greatly across disorders, disease stages, and applied quantification methods. To advance TSPO PET as a potential biomarker to evaluate brain inflammation and anti-inflammatory therapies, a better understanding of its applicability across disorders is needed. We conducted a transdiagnostic systematic review and meta-analysis of all in vivo human TSPO PET imaging case-control studies in the CNS. Specifically, we investigated the direction, strength, and heterogeneity associated with the TSPO PET signal across disorders in pre-specified brain regions, and explored the demographic and methodological sources of heterogeneity. We searched for English peer-reviewed articles that reported in vivo human case-control TSPO PET differences. We extracted the demographic details, TSPO PET outcomes, and technical variables of the PET procedure. A random-effects meta-analysis was applied to estimate case-control standardized mean differences (SMD) of the TSPO PET signal in the lobar/whole-brain cortical grey matter (cGM), thalamus, and cortico-limbic circuitry between different illness categories. Heterogeneity was evaluated with the I2 statistic and explored using subgroup and meta-regression analyses for radioligand generation, PET quantification method, age, sex, and publication year. Significance was set at the False Discovery Rate (FDR)-corrected P < 0.05. 156 individual case-control studies were included in the systematic review, incorporating data for 2381 healthy controls and 2626 patients. 139 studies documented meta-analysable data and were grouped into 11 illness categories. Across all the illness categories, we observed a significantly higher TSPO PET signal in cases compared to controls for the cGM (n = 121 studies, SMD = 0.358, P FDR < 0.001, I2 = 68%), with a significant difference between the illness categories (P = 0.004). cGM increases were only significant for Alzheimer's disease (SMD = 0.693, P FDR < 0.001, I2 = 64%) and other neurodegenerative disorders (SMD = 0.929, P FDR < 0.001, I2 = 73%). Cortico-limbic increases (n = 97 studies, SMD = 0.541, P < 0.001, I2 = 67%) were most prominent for Alzheimer's disease, mild cognitive impairment, other neurodegenerative disorders, mood disorders and multiple sclerosis. Thalamic involvement (n = 79 studies, SMD = 0.393, P < 0.001, I2 = 71%) was observed for Alzheimer's disease, other neurodegenerative disorders, multiple sclerosis, and chronic pain and functional disorders (all P FDR < 0.05). Main outcomes for systemic immunological disorders, viral infections, substance use disorders, schizophrenia and traumatic brain injury were not significant. We identified multiple sources of between-study variance to the TSPO PET signal including a strong transdiagnostic effect of the quantification method (explaining 25% of between-study variance; V T -based SMD = 0.000 versus reference tissue-based studies SMD = 0.630; F = 20.49, df = 1;103, P < 0.001), patient age (9% of variance), and radioligand generation (5% of variance). This study is the first overarching transdiagnostic meta-analysis of case-control TSPO PET findings in humans across several brain regions. We observed robust increases in the TSPO signal for specific types of disorders, which were widespread or focal depending on illness category. We also found a large and transdiagnostic horizontal (positive) shift of the effect estimates of reference tissue-based compared to V T -based studies. Our results can support future studies to optimize experimental design and power calculations, by taking into account the type of disorder, brain region-of-interest, radioligand, and quantification method. [ABSTRACT FROM AUTHOR]