Furthermore, we have shown that expression of Aβ in glutamatergic neurons results in progressive, age-dependent, neurodegeneration modulated by endocytic and endosomal regulators, including the established AD modifier PICALM (Griffin et al., 2018; Treusch et al., 2011), and is amenable to pharmacological treatment (Matlack et al., 2014; Tardiff et al., 2017). This evidence concerns the gene PICALM and Alzheimer disease.