Taking into consideration Aβ and Tau PET findings together with our data, we propose a neurodegeneration model for PSEN1 E280A carriers where disturbed Aβ production and accumulation are the prerequisite for developing dementia, while other factors, such as altered protein degradation affecting Tau phosphorylation, are important modifiers accelerating disease kinetics and cognitive decline. This evidence concerns the gene PSEN1 and dementia.