Autoantibody pathogenicity in antibody-induced and common neurodegenerative diseases

自身抗体疾病可以表现出类似于原发和继发性tauopy病的病理变化，即阿尔茨海默病和FTD-tau变异体，其特征是轴突微管相关蛋白tau(MAPT)在神经元内的错误分类、聚集和聚集。在其他FTD变异型和肌萎缩侧索硬化症中，核TDP-43蛋白的胞浆聚集是驱动神经毒性的主要病理因素。自身抗体与tau和TDP-43异常之间的神经生物学关系尚不清楚。我们致力于确定tau/TDP-43、自身抗体和神经变性之间的分子和细胞联系，并将调查tau/TDP-43错误分类和聚集是否由自身抗体触发，以及tau是否在自身抗体疾病中起到神经毒性的中介作用，类似于阿尔茨海默病、tauopathy和其他导致神经元退化的大脑应激状况。此外，我们将阐明自身抗体对个体和网络神经元功能的影响。

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.