PSEN1 and Alzheimer disease: Similarly, CX-4945 strongly inhibited the phosphorylation of APP and PS1, which are also well-known substrates of DYRK1A and are crucial for amyloid plaque formation in DS and AD (Ryu et al., 2010; Smith et al., 2012), with estimated IC50 values of ∼80 and 100 nM for APP and PS1, respectively (Fig. 4).