In DS it has been observed that both neurofibrillary tau deposition16 and cognitive decline27,28 occur rapidly following the onset of amyloid, with some estimates showing change as early as 5 years after PET A+ is reached.19 The rapid onset of tau and cognitive decline suggests that a narrow window of opportunity exists to treat AD in DS, highlighting that age-based clinical trial recruitment alone is not sufficient. Here, MAPT is linked to Mental deterioration.