MAPT and Alzheimer disease: To substantiate, while it has been shown that reduction of Aβ protein levels in the CSF precedes that of tau aggregates by many years, the accumulation of tau with AD relevant phosphorylation epitopes takes place decades before Aβ plaque formation (Motter et al., 1995; Braak et al., 2011, 2013; Musiek and Holtzman, 2012).