A longitudinal biomarker study of Patients with Corticobasal Syndrom: Activity of Cerebral Networks, Amyloid and Microglia in Aging and Alzheimer's disease (ActiGliA) – In vivo Imaging of Microglial Activation by TSPO PET

Ziel/Aim:

Corticobasal Syndrome (CBS) is a rare clinical condition with heterogeneous underlying diseases. The most frequent neuropathological diagnoses of CBS patients are either the 3R/4R tauopathy Alzheimer's disease (AD) or the 4R tauopathies Corticobasal Degeneration (CBD) and Progressive Supranuclear Palsy (PSP). Microglia, the cerebral innate immune cells, have been shown to be dysfunctional in AD, CBD and PSP. In our interdisciplinary study “Activity of Cerebral Networks, Amyloid and Microglia in Aging and Alzheimer's Disease (ActiGliA)”, we generate multimodal prospective imaging and fluid biomarker data in CBS patients. Here we want to focus on TSPO-PET, which is a biomarker for microglial activity.

Methodik/Methods:

Until now 15 patients (69 ± 7; 7 f/8 m) with probable CBS according to current diagnosis criteria underwent F-18-GE180 TSPO-PET. All images were scaled by the global mean and standardized uptake value ratios (SUVR) were generated in brain regions typically affected in CBS. Seven healthy individuals (HC) served as controls. amyloid PET was already performed in 12 out of 15 patients.

Ergebnisse/Results:

Significantly increased TSPO SUVR in CBS versus HC were observed in the Thalamus of both sides (left: +23%, p < 0.005; right: +27%, p < 0.01), in the right Pallidum (+9%, p < 0.05) and in the anterior cingulate Cortex on both sides (left: +15%, p < 0.05; right: +13%, p < 0.05). Furthermore we found increased microglial activation in the hippocampus on both sides (left: +13%, p < 0.05; right: +13%, p < 0.05). Preliminary findings of amyloid positive CBS patients (N = 3) indicated higher microglial activity than amyloid negative patients (N = 9) in the frontal lobe (+10%; p < 0.01).

Schlussfolgerungen/Conclusions:

CBS patients have elevated microglial activation in cortical and subcortical areas, pronounced in the thalami. The higher microglial activity in the frontal cortex of amyloid positive patients needs further investigation and may serve for deeper understanding of amyloid and tau contributions to microglial activation.