MAPT and Alzheimer disease: Previous studies have shown that tau is primarily secreted in its free form, with a minor fraction found in EVs, as observed in the CSF and blood of both control subjects and AD patients (Arai et al. 1998; Saman et al. 2012; Zetterberg et al. 2013; Fiandaca et al. 2015; Ruan and Ikezu 2020; Brunello et al. 2020).