MAPT and Alzheimer disease: Abu-Rumeileh et al. (2025) documented increased serum p-tau217 and p-tau181 concentrations in ALS patients, which resemble markers of AD. Importantly, these phosphorylated tau variants were identified in muscle biopsies from ALS patients and localized to atrophic fibers using immunohistochemistry and mass spectrometry techniques. This peripheral source of p-tau challenges the CNS-centric perspective of tau pathology and raises intriguing questions about common phosphorylation mechanisms in both the central and peripheral nervous systems (Abu-Rumeileh et al., 2025).