Specifically, it remains unclear (1) how baseline and longitudinal plasma p-tau181 is associated with progressive AD-specific neurodegeneration; (2) whether plasma p-tau181 provides complementary information to non–disease-specific plasma biomarkers of neurodegeneration, such as neurofilament light chain (NfL)20,21,22; and (3) how imaging neurodegeneration markers mediate the association between plasma p-tau181 and cognitive decline. Here, NEFL is linked to Alzheimer disease.