PRNP and Alzheimer disease: Interestingly, APP and PrPc, which are able to interact with each other and with many other proteins, including Aβ, tau, the ECM, adhesion molecules, cell cytoskeleton [41,180,181,182,183,184,185], are significantly co-upregulated in brain EVs from AD patients compared to age-matched controls specifically in the preclinical stages of the disease, suggesting their implication in disease onset and/or early development [95].