Phosphorylation, "missorting", and aggregation are hallmark pathological changes in Tauopathies, including Alzheimer’s disease. SImilar Tau changes also occurr during neuronal stress reactions. To understand how, and what for, Tau phospohrylation and missorting occur, we utilize autoimmune-antibodies that trigger Tau pathology, e.g. in IgLON5 disease. Our findings reveal a role of neuronal hyperactivity as inducer of Tau changes that later can manisfest as Tau pathology. A similar mechanism is suggested for AD. Our data therefore suggest that mis-tuning of neuronal network activity is common path to Tau pathology across neurological disease spectra, and that autoimmune antibodies offer a well-controlled experimental system to study Tau ‚reactions‘ in this context.