APP and Alzheimer disease: Another Hsa21 gene, USP25, has been implicated to contribute to the worsened AD-DS neuroinflammation in the Dp(16)1Yey mouse, whereby overexpression of this gene in the 5XFAD mouse model of AD caused increase microglial activation, loss of neuronal spines and worsened cognition (Zheng et al., 2021); as previously mentioned, this may occur indirectly via an effect on APP processing (Zheng et al., 2022).