Robust Increase in <scp>IQCK</scp> Protein Expression in Mouse Models of Alzheimer's Disease and <scp>iPSC</scp>‐Derived Neurons

Emerging studies indicate that the IQ-motif-containing protein K (IQCK) is a novel risk factor for Alzheimer's disease (AD), an age-associated disease. The expression patterns of IQCK in healthy and AD brains, within the context of age and sex are largely unknown. Therefore, we compared the age-dependent expression patterns of IQCK in males and females of wild-type (WT) mice with AD-like 3xTg and APΔE9 mice. Additionally, we measured IQCK protein expression in AD-derived human iPSC neurons. In WT mice, we found no IQCK expression at day 1 (1D) in the cortex (CX), hippocampus (HP), brainstem (BS) and cerebellum (CB). Overall, IQCK protein expression in different brain regions was first detected in 1-month-old wild-type (WT) mice, reaching its maximum in 1-year-old mice (1Y), and then gradually decreased in 2-year-old mice. In the APΔE9 mice, IQCK protein levels significantly increased by 1246% in the CX, 682% in the HP and 169% in the BS relative to WT controls. In the 3xTg mice, only HP showed an increase of IQCK protein by 277%. In addition, we also detected elevated tendencies in BS and CB regions but not in the CX. Finally, IQCK expression was also significantly increased by 68% in the AD-derived iPSC neurons relative to the NC-derived iPSC neurons. Thus, increased IQCK protein levels in the brain of AD-like 3xTg and APΔE9 mouse models suggest a possible role in AD pathogenesis, a finding that requires further clarification.