PSEN1 and Alzheimer disease: As we mentioned, early stages of AD brain pathology are associated with tau protein phosphorylation at several amino acids residues such as Thr231 and Thr181, as well as with increased levels of PHF-1 and total tau (Figure 4) not only in brain cells but also in cells from peripheral tissues such as submandibular gland, sigmoid colon, liver, scalp and abdominal skin (Dugger et al., 2016), which supports our finding that FAD fibroblast showed enhanced tau phosphorylations at these epitopes, events that could be associated with PS1 mutations that affect ERK1/2 and GSK3 expression or activity.