Previous studies have shown that the CypA/MMP9 signaling pathway is responsible for BBB breakdown and subsequent cognitive decline, thus the blockade of CypA/MMP9 signaling can restore BBB integrity and normalize the function of neurons and synapses (Bell et al., 2012; Halliday et al., 2016; Montagne et al., 2020). This evidence concerns the gene PPIA and Mental deterioration.