In this study, we compare tau accumulation, tau spreading, tau-mediated inflammation and neurodegeneration in isogenic human iPSC derived astrocytes, homozygous for APOEε2 and APOEε4. The experimental set-up was based on the fact that APOEε4 is the greatest genetic risk factor for developing AD, while APOEε2 is a significant risk factor for developing other diseases, including PSP, AGD, and CAA. This evidence concerns the gene MAPT and argyrophilic grain disease.