Guam amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) features CTE-like tau seeds in brain and spinal cord

Neurodegenerative tauopathies are characterized by proteinaceous deposits containing microtubule-associated tau in nervous tissue. Emerging evidence suggests that disease-associated tau proteins adopt abnormal, self-propagating conformations characteristic of prions. Here, we employed alanine mutational scanning (Ala scan) to determine the nature of prion-like tau seeds in ALS/PDC, a mysterious disorder that occurred formerly in high incidence in certain regions in the western Pacific. We show that the Ala scan incorporation profile of ALS/PDC tau is similar to that of abnormal tau proteins in chronic traumatic encephalopathy (CTE). The findings lend support to the idea that ALS/PDC can be classified structurally as a CTE-like tauopathy. This work may have important implications for our understanding of ALS/PDC as well as common neurological disorders beyond the Pacific.