Given that NEP expression invariably declines with age (Iwata et al, 2002; Wang et al, 2003; Russo et al, 2005; Hellstrom-Lindahl et al, 2008), it is notable that even heterozygous Mme deficiency, presenting an ∼50% reduction in NEP activity (Iwata et al, 2001), thus resulted in a relative increase in the ratio of Aβ3pE-40/42 to Aβ1-40/42 (Fig 2D). The gene discussed is MME; the disease is hyperinsulinemic hypoglycemia, familial, 4.