Lipocalin 2 contributes to brain iron dysregulation but does not affect cognition, plaque load, and glial activation in the J20 Alzheimer mouse model

Abstract Background Lipocalin 2 (Lcn2) is an acute-phase protein implicated in multiple neurodegenerative conditions. Interestingly, both neuroprotective and neurodegenerative effects have been described for Lcn2. Increased Lcn2 levels were found in human post-mortem Alzheimer (AD) brain tissue, and in vitro studies indicated that Lcn2 aggravates amyloid-β-induced toxicity. However, the role of Lcn2 has not been studied in an in vivo AD model. Therefore, in the current study, the effects of Lcn2 were studied in the J20 mouse model of AD. Methods J20 mice and Lcn2-deficient J20 (J20xLcn2 KO) mice were compared at the behavioral and neuropathological level. Results J20xLcn2 KO and J20 mice presented equally strong AD-like behavioral changes, cognitive impairment, plaque load, and glial activation. Interestingly, hippocampal iron accumulation was significantly decreased in J20xLcn2 KO mice as compared to J20 mice. Conclusions Lcn2 contributes to AD-like brain iron dysregulation, and future research should further explore the importance of Lcn2 in AD.