To create a mouse model that recapitulates features of PICALM reduction in AD [28, 31, 32], we crossed Picalm+/− mice [28, 53] to the 5XFAD mouse line [54] and generated Picalm-deficient Picalm+/−; 5XFAD model with elevated Aβ pathology compared to age-matched 5XFAD littermates as shown by increased Aβ42 and Aβ40 levels in the hippocampus and cortex by 78 and 64% (Aβ42), and 160 and 130% (Aβ40), respectively, and increased Aβ load and thioflavin S-positive plaque load in the hippocampus and cortex by 78 and 67% (Aβ load), and 101 and 108% (thioflavin S load), respectively (Fig. S2). The gene discussed is PICALM; the disease is Alzheimer disease.