NEFL and Mental deterioration: For people in the early stages of sporadic AD, elevated levels of plasma p-tau217, p-tau181, and NfL are associated with cognitive decline over time and conversion to AD dementia,15,16,37,38 whereas in DS, baseline and longitudinal changes in plasma NfL have been linked to the progression of cognitive symptoms.9,39 Our study demonstrated that at a cross-sectional level, high plasma p-tau217 concentration was independently associated with worse cognitive performance in participants with DS.