Calmodulin-like skin protein is downregulated in human cerebrospinal fluids of Alzheimer’s disease patients with apolipoprotein E4; a pilot study using postmortem samples

AbstractObjective: Calmodulin-like skin protein (CLSP) is a secreted peptide that inhibits neuronal cell death, linked to Alzheimer’s disease (AD), by binding to the heterotrimeric humanin receptor and activating an intracellular survival pathway. CLSP is only expressed in skin keratinocytes and related epithelial cells, circulates in the blood stream, and passes the blood–cerebrospinal fluid (CSF) barrier. In the current study, we addressed the issues as to whether CLSP functions in the central nervous system and whether the concentration of CLSP is reduced in the CSFs of AD patients.Methods: Mice were intraperitoneally injected with 5 nmol of recombinant human CLSP. At 1h after the injection, the mice were sacrificed for the analysis of the existence of human CLSP in blood and interstitial fluid (ISF)-containing brain samples. Using postmortem CSF samples, we next determined the concentrations of CLSP in CSFs of human AD and control cases.Results: Intraperitoneally administered recombinant human CLSP ci...