The physiological Aβ(1–40) peptide accounts for ~ 90% of the pool, but the contribution of Aβ(1–42) increases significantly in the Alzheimer disease (AD) brain2 and likely reflects relative shifts in α-, β- and γ-secretase-mediated cleavage of the Amyloid Protein Precursor (APP)3. Here, XPNPEP3 is linked to Alzheimer disease.