Impact of IgLON5 on cerebellar circuits and pathology

Anti-IgLON5 disease is associated with autoantibodies against the cell-adhesion molecule IgLON5 and characterized by sleep abnormality and brainstem dysfunction. Studies on autopsy tissue revealed a peculiar tauopathy in brainstem and hypothalamus in some patients while others only show mild inflammatory infiltrates with variable deposits of IgG1 and IgG4. The mechanisms how anti-IgLON5 antibodies cause neuronal dysfunction that may result in tauopathy remains largely unknown. We will therefore investigate post-mortem tissue of 9 IgLON5 patients, 6 with and 3 without tauopathy and stain for inflammation to study the impact of anti-IgLON5 antibodies on neurons and their synapses and elucidate the connex between inflammation and neurodegeneration. Furthermore we will investigate the effects of different anti-IgLON5 antibody subclasses (IgG1, IgG4) in live cultures of hippocampal neurons, to gain insights into the pathomechanisms of neuronal dysfunction. The understanding of the pathomechanisms in anti-IgLON5 disease will help to develop treatment strategies and get more insights in the processes that induce neurodegnerative diseases.