Neuronal Hyperacitivity Triggers Severe Autoimmune Brain Disorder
Researchers unravel effects of autoimmune antibodies in “IgLON5 Encephalitis” and see similarities to Alzheimer’s disease mechanisms
Berlin (Germany), May 13, 2026.In a condition known as “IgLON5 encephalitis”, the immune system mistakenly attacks cells in the brain. This leads to brain inflammation and neuronal damage, which can manifest as sleep disturbances, cognitive impairment, and movement disorders. Researchers at DZNE and Charité – Universitätsmedizin Berlin have now identified fundamental mechanisms underlying this rare but severe neurodegenerative disease. Their findings, based on applying antibodies from affected individuals in neuronal cell cultures and mice, have been published in the journal “Science Advances”.
The disease involves rogue antibodies directed against a cell surface protein called IgLON5. However, until now it was unclear, how this interaction gives rise to a hallmark of the disease. Namely, how the antibodies lead to aggregation of another protein known as “Tau”. “Now, we found that the aberrant antibodies cause IgLON5 proteins to cluster with other molecules on the cell surface. This triggers abnormal neuronal hyperactivity and a fatal cascade that ultimately results in Tau mislocalization and aggregation. In other words, our findings establish a causal link between the IgLON5 antibodies and Tau pathology”, Prof. Susanne Wegmann, a research group leader at DZNE and Charité, explains. Tau proteins that detach from the cytoskeleton and aggregate can initiate cell toxicity and ultimately neuronal degeneration. Pathological Tau protein aggregation also plays a major role in Alzheimer’s disease: There, too, neuronal hyperactivity – in that case triggered by misfolded amyloid-beta proteins – is suspected to induce pathology Tau changes. “These similarities will now need to be examined more closely”, says Wegmann.
A potential treatment approach
The specific form of encephalitis currently under investigation, also known as “Anti-IgLON5 disease”, was first documented in 2014 and is quite rare. Due to its complex phenotype, which includes a wide range of possible symptoms, the disease tends to escape early diagnosis. Current treatments options comprise immunosuppression, dialysis, and other approaches. The disease leads to severe disabilities, if untreated, and may result in premature death. “Our findings identified neuronal hyperactivity as a driver of the disease. This aspect was previously unknown. Alleviating this dysfunction could be a target for future therapies,” the Berlin biophysicist concludes.
Original publication
IgLON5 autoimmune antibodies activate Tau via neuronal hyperactivity
Bilge Askin et al.
Science Advances (2026).
DOI: 10.1126/sciadv.aec2042