PET studies show that cortical Aβ burden needs to surpass a critical threshold prior to spreading of tau pathology from medial temporal lobes to the neocortex, accelerating cognitive deterioration.15 The sequence of pathologies suggests that targeting Aβ should ameliorate downstream tau pathology and cognitive decline, as observed in clinical trials involving aducanumab, lecanemab and donanemab.16-19. This evidence concerns the gene MAPT and Mental deterioration.