Autoantibody pathogenicity in antibody-induced and common neurodegenerative diseases

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Autoantibody diseases can display pathological changes reminiscent of primary and secondary tauopathies, i.e, Alzheimer’s disease and FtD-tau variants, which are characterized by intraneuronal “missorting”, accumulation, and aggregation of the axonal microtubule associated protein tau (maPt). in other FtD variants and amyotrophic lateral sclerosis, the cytosolic aggregation of nuclear tDP-43 protein is the major pathology thought to drive neurotoxicity. the neurobiological relation between autoantibodies and tau and tDP-43 abnormalities is not known. We strive to identify the molecular and cellular link between tau/tDP-43, autoantibodies, and neurodegeneration, and will investigate whether tau/tDP-43 missorting and aggregation is triggered by autoantibodies, and whether tau functions as mediator of neurotoxicity in autoantibody diseases, similar to Alzheimer’s disease, tauopathies, and other brain stress conditions leading to neurondegeneration. Furthermore, we will clarify the impact of autoantibodies on individual and network neuronal function.