In conclusion, our study identifies TSPAN6, a moderately up-regulated gene in the prefrontal cortex of AD patients, as a new modulator of APP-CTF proteostasis preventing its degradation by the impairment of the autolysosomal pathway, leading to consequent enhanced Aβ production, and turning the balance towards the formation of ILVs destined to form exosomes (Fig. 8 h). This evidence concerns the gene APP and Alzheimer disease.