In addition, cotinine has shown to reduce the activation of macrophages (Rehani et al., 2008) and be neuroprotective, reducing plaque deposition, tau hyperphosphorylation, and cognitive impairment while increasing the expression of the postsynaptic density protein 95 (PSD95) in transgenic AD mice overexpressing human Aβ peptides (Terry et al., 2005, 2012, 2015; Echeverria et al., 2011; Echeverria and Zeitlin, 2012; Patel et al., 2014; Grizzell et al., 2017). This evidence concerns the gene DLG4 and Alzheimer disease.