These findings reinforce the notion that mitochondrial quality control and retrograde signaling are tightly coupled and that disruption of mitochondrial homeostasis by pathological proteins such as tau can lead to broader cellular reprogramming, a concept further supported by evidence showing that the activation of the mitochondrial unfolded protein response (UPRmt) exerts a protective role against Aβ proteotoxicity in mammalian systems [42, 43], highlighting conserved mitochondria-to-nucleus communication pathways present in Alzheimer’s disease. This evidence concerns the gene MAPT and early-onset autosomal dominant Alzheimer disease.