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Autoimmune encephalitis and neurodegenerative disorders share several clinical features, including behavioural and psychiatric manifestations, cognitive impairment, sleep and movement disorders. Therefore, it is not surprising that autoimmune encephalitis is one of the main differential diagnoses of rapidly progressive dementia. However, more chronic presentations of autoimmune disorders have been reported and can lead to the misdiagnosis of a neurodegenerative disease. On the other hand, antibodies against neuronal proteins, such as those directed against NMDAR, can occur during established neurogenerative disorders, and their role in this context is still unclear. They might be simple bystanders or modify the disease course and phenotype. Indeed, autoimmune encephalitis can leave long-term cognitive sequelae and specific antibodies to neuronal surface antigens are associated with clinical and pathological neurodegenerative features. Here we review the link between these antibodies and neurodegeneration. In particular we discuss: (a) the possibility that autoimmune encephalitis presents as a neurodegenerative disease, identifying the red flags that can help in the differential diagnosis between antibody-mediated and neurodegenerative disorders; (b) the occurrence of antibodies against neuronal surface antigens in patients with neurodegenerative disorders and their possible role in the disease course; and (c) the long-term cognitive and neuroradiological changes associated with autoimmune encephalitis, as well as the biomarkers that can help to predict the cognitive outcome. Finally, we review the clinical and pathological features of IgLON5 antibodies-related encephalitis, a unique model of the relationship between antibodies and neurodegeneration.

The neuromuscular junction (NMJ) is the target of a variety of immune-mediated disorders, usually classified as presynaptic and postsynaptic, according to the site of the antigenic target and consequently of the neuromuscular transmission alteration. Although less common than the classical autoimmune postsynaptic myasthenia gravis, presynaptic disorders are important to recognize due to the frequent association with cancer. Lambert Eaton myasthenic syndrome is due to a presynaptic failure to release acetylcholine, caused by antibodies to the presynaptic voltage-gated calcium channels. Acquired neuromyotonia is a condition characterized by nerve hyperexcitability often due to the presence of antibodies against proteins associated with voltage-gated potassium channels. This review will focus on the recent developments in the autoimmune presynaptic disorders of the NMJ.