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Liver-expressed antimicrobial peptide 2 elevation contributes to age-associated cognitive decline
dc.contributor.author | Tian, Jing | |
dc.contributor.author | Guo, Lan | |
dc.contributor.author | Wang, Tienju | |
dc.contributor.author | Jia, Kun | |
dc.contributor.author | Swerdlow, Russell H. | |
dc.contributor.author | Zigman, Jeffrey M. | |
dc.contributor.author | Du, Heng | |
dc.date.accessioned | 2023-08-14T16:23:54Z | |
dc.date.available | 2023-08-14T16:23:54Z | |
dc.date.issued | 2023-05-22 | |
dc.identifier.citation | Tian, J., Guo, L., Wang, T., Jia, K., Swerdlow, R. H., Zigman, J. M., & Du, H. (2023). Liver-expressed antimicrobial peptide 2 elevation contributes to age-associated cognitive decline. JCI insight, 8(10), e166175. https://doi.org/10.1172/jci.insight.166175 | en_US |
dc.identifier.uri | https://hdl.handle.net/1808/34730 | |
dc.description.abstract | Elderly individuals frequently report cognitive decline, while various studies indicate hippocampal functional declines with advancing age. Hippocampal function is influenced by ghrelin through hippocampus-expressed growth hormone secretagogue receptor (GHSR). Liver-expressed antimicrobial peptide 2 (LEAP2) is an endogenous GHSR antagonist that attenuates ghrelin signaling. Here, we measured plasma ghrelin and LEAP2 levels in a cohort of cognitively normal individuals older than 60 and found that LEAP2 increased with age while ghrelin (also referred to in literature as “acyl-ghrelin”) marginally declined. In this cohort, plasma LEAP2/ghrelin molar ratios were inversely associated with Mini-Mental State Examination scores. Studies in mice showed an age-dependent inverse relationship between plasma LEAP2/ghrelin molar ratio and hippocampal lesions. In aged mice, restoration of the LEAP2/ghrelin balance to youth-associated levels with lentiviral shRNA Leap2 downregulation improved cognitive performance and mitigated various age-related hippocampal deficiencies such as CA1 region synaptic loss, declines in neurogenesis, and neuroinflammation. Our data collectively suggest that LEAP2/ghrelin molar ratio elevation may adversely affect hippocampal function and, consequently, cognitive performance; thus, it may serve as a biomarker of age-related cognitive decline. Moreover, targeting LEAP2 and ghrelin in a manner that lowers the plasma LEAP2/ghrelin molar ratio could benefit cognitive performance in elderly individuals for rejuvenation of memory. | en_US |
dc.publisher | American Society for Clinical Investigation | en_US |
dc.rights | © 2023, Tian et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License. | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
dc.subject | Aging | en_US |
dc.subject | Neuroscience | en_US |
dc.subject | Alzheimer's disease | en_US |
dc.subject | Coupled receptors | en_US |
dc.subject | Memory | en_US |
dc.title | Liver-expressed antimicrobial peptide 2 elevation contributes to age-associated cognitive decline | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Guo, Lan | |
kusw.kuauthor | Du, Heng | |
kusw.kudepartment | Higuchi Biosciences Center | en_US |
dc.identifier.doi | 10.1172/jci.insight.166175 | en_US |
kusw.oaversion | Scholarly/refereed, publisher version | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.rights.accessrights | openAccess | en_US |