Objective: The purpose of this prospective cohort study is to analyse the topographical and temporal relationship between cerebral microglia activity changes, network degeneration and atrophy in context of CSF and blood biomarkers over 18 months disease course.

Background: Corticobasal Syndrome (CBS) is a rare clinical condition defined by signs and symptoms of cortex and basal ganglia dysfunction.  Neuropathological diagnoses in CBS most frequently are the 3-repeat/4-repeat tauopathy Alzheimer’s disease (AD; 25%), or the 4-repeat tauopathies Corticobasal Degeneration (CBD) and Progressive Supranuclear Palsy (PSP), respectively. Ante-mortem diagnosis of these entities is challenging. Biomarkers are needed to establish a reliable diagnosis and to track disease progression. Microglia have been shown to be dysfunctional in AD, CBD and PSP. However, the chronology of microglia dysfunction, cerebral atrophy and functional and structural connectivity remains unclear.

Method: We aim to generate comprehensive clinical assessment, multimodal prospective in vivo imaging and blood and CSF biomarker data in 30 CBS patients, fulfilling either the MDS criteria for suggestive or possible PSP-CBS or the Armstrong Clinical Research criteria for possible or probable CBD-CBS. TSPO PET (18F-GE180) targets the 18kDa translocator protein expressed in activated microglia. 18F-Flutemetamol PET is used to detect β-Amyloid depositions indicative of possible AD pathology. MPRAGE, DTI and RS-fMRI demonstrate structural and functional connectivity as well as regional atrophy in the brain. Patients are examined at baseline and after 18 months. This cohort is embedded in the interdisciplinary AD study “Activity of Cerebral Networks, Amyloid and Microglia in Aging and Alzheimer‘s Disease”.

Results: So far, 26 patients have been recruited. We will show cross-sectional baseline results. In our cohort, we have identified less AD typical pathology in CSF and imaging than expected (15%). TSPO PETs showed microglial activation in 96%.

Conclusion: With this study, chronological and topographical relationship of microglia activation, cerebral atrophy and changes in functional and structural connectivity in CBS are explored in a multimodal manner. We aim to further understand the role of neuroinflammation in the pathogenesis of CBS and its pathological sub-forms, with either underlying AD-pathology or 4R-tauopathy.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/activity-of-cerebral-networks-amyloid-and-microglia-in-corticobasal-syndrome-the-actiglia-study/