GRN and Alzheimer disease: Studies using APPswe/PS1∆E9 and 5XFAD mouse models of amyloid pathology have shown that constitutive loss of PGRN has no exacerbating effects on Aβ pathology [52, 182], which is consistent with human ADNI biomarker data showing no effects of the GRN rs5848 AD variant on amyloid pathology [52].