DYRK1A and Alzheimer disease: If DYRK1A regulates Ca2+, its overexpression could contribute to the Ca2+ surge observed in AD astrocytes (Delekate et al., 2014; Haughey and Mattson, 2003; Kuchibhotla et al., 2009; Sompol et al., 2017; Takano et al., 2007), establishing a positive feedback loop to prolong astrocyte reactivity over time, where elevated Ca2+ and sustained calpain-dependent DYRK1A overactivation continuously upregulate STAT phosphorylation while also promoting Ca2+ mobilization, reinforcing this loop (Figure 3G).