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.
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About Deutsches Zentrum für Neurodegenerative Erkrankungen, DZNE (German Center for Neurodegenerative Diseases): DZNE is one of the world’s leading research centers for neurodegenerative diseases such as Alzheimer’s, Parkinson’s and ALS, which are associated with dementia, movement disorders and other serious health impairments. These diseases place an enormous burden on patients and their families, but also on society and the economy of healthcare. DZNE contributes significantly to the development and translation into practice of novel strategies for prevention, diagnosis, care and treatment. DZNE comprises ten sites across Germany and collaborates with universities, university hospitals, research centers and other institutions in Germany and throughout the world. DZNE is state-funded and a member of the Helmholtz Association and of the German Centers for Health Research.
Science Advances
Experimental study
Cells
IgLON5 autoimmune antibodies activate Tau via neuronal hyperactivity
13-May-2026