For example, notable differences between Picalm-deficient A7 mice compared to 5XFAD model of Picalm deficiency are that A7 mice develop pathology at a much slower rate than 5XFAD mice with Aβ42/Aβ40 ratio of over 100:1, in contrast to 5XFAD mice with five familial AD mutations (3 in APP: Swedish, Florida, London; and 2 in presenilin 1 (PS1): M146L+ L286V), that develop Aβ pathology much earlier with Aβ42/Aβ40 ratio typically on the order of 10–20:1 [50, 54, 79]. This evidence concerns the gene PSEN1 and hyperinsulinemic hypoglycemia, familial, 4.