This notion is supported by biomarker studies in sporadic AD patients demonstrating that a decrease in CSF Aβ42 was the earliest change reported (Skoog et al., 2003; Gustafson et al., 2007), while in patients with familial AD reductions in CSF Aβ42 and elevations in tau occur around 10–15 years prior to symptom development (Bateman et al., 2012; Ringman et al., 2012). Here, MAPT is linked to Alzheimer disease.