MAPT and neurodegenerative disease: Table 2 shows that the vast majority of patients with MAPT variants, with the exceptions of R5L, V363I, and V363A, have a family history of Parkinsonian syndrome, dementia, or other neurodegenerative diseases. This supports the previously published notion of familial clustering in PSP (27, 51). Clinical heterogeneity has been observed even among patients carrying the same variant, including those within the same family, underscoring the complex interaction of genetic and environmental factors in PSP (33, 34, 37).