The combination of GFAP, p-tau217, p-tau231, and p-tau181 achieved an AUC of 0.900 (95% CI, 0.811–0.989) in distinguishing individuals with preNIID from HCs, indicating that p-tau and GFAP alterations are early indicators of NIID pathogenesis. Here, MAPT is linked to neuronal intranuclear inclusion disease.