An elegant study carried out on a novel APP knock-in mouse model (AppSAA) of AD with three mutations (Austrian, Swedish, and Arctic) in the mouse APP gene, showed significant alterations regarding lipid metabolism and disease-associated transcriptomic signature in the microglia containing a high amount of intracellular βA, consisting of vascular amyloid deposits, an accumulation of parenchymal amyloid plaques, alteration of astroglial and microglial functions, and an increase in CSF markers of neurodegeneration. This evidence concerns the gene APP and amyloidosis.