PSEN1 and familial Alzheimer disease: Remarkably, those early onset familial Alzheimer’s disease (FAD)-linked PSEN1 mutations lead to increased molar ratios of Aβ42 over Aβ40 in cell lines and in the brains of transgenic animals, as well as in the plasma of FAD patients with PSEN1 mutations, compared with controls [10,11,12].