For example, changes in CSF tau levels have been shown to develop ~15 years before the onset of clinical AD, while CSF Aβ42 levels may drop even earlier, up to 20 years before symptom onset (Bateman et al., 2012; Buchhave, 2012; Villemagne et al., 2013; Fagan et al., 2014). This evidence concerns the gene MAPT and Alzheimer disease.