Although a relative ratio of longer to shorter Aß peptides (often the Aß-42/40 ratio) has become a more widely accepted AD biomarker (Tanzi & Bertram, 2005; Selkoe & Hardy, 2016; Hampel et al, 2021), it is worth noting that not all familial AD-causing mutations lead to increased relative or absolute Aß-42 production, including many PSEN1 mutations that impair net γ-secretase activity and thus reduce production of both Aß species (Sun et al, 2017). Here, PSEN1 is linked to Alzheimer disease.