title: The Orphan C2orf40 Gene is a Neuroimmune Factor in Alzheimer's Disease.
abstract: Expression of the orphan C2orf40 gene is associated with the aggregation of the neurofibrillary tangle-protein tau in transgenic mice, tumor suppression, the induction of senescence in CNS, and the activation of microglia and peripheral mononuclear leukocytes. This gene also encodes several secreted pro- and anti-inflammatory neuropeptide-like cytokines, suggesting they might be implicated in the inflammatory component(s) of Alzheimer's disease (AD). Accordingly, we evaluated human AD and control brains for expression changes by RT-qPCR, Western blot, and histological changes by immunolabeling. RT-qPCR demonstrated increased cortical gene expression in AD. The molecular form of Ecrg4 detected in cortex was 8-10 kDa, which was shown previously to interact with the innate immunity receptor complex. Immunocytochemical studies showed intensely stained microglia and intravascular blood-borne monocytes within cerebral cortical white matter of AD patients. Staining was diminished within cortical neurons, except for prominent staining in neurofibrillary tangles. Choroid plexuses showed a decreasing trend. These findings support our hypothesis that c2orf40 participates in the neuroimmune response in AD.
authors.affiliation: Department of Surgery, University of California San Diego School of Medicine, USA; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, USA.
authors.forename: Sonia
authors.initials: S
authors.lastname: Podvin
authors.affiliation: Department of Pathology, Rhode Island Hospital, USA; Department of Neurosurgery, Warren Alpert Medical School of Brown University, USA.
authors.forename: Miles C
authors.initials: MC
authors.lastname: Miller
authors.affiliation: Department of Pathology, Rhode Island Hospital, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Rossi
authors.affiliation: Department of Pathology, Rhode Island Hospital, USA.
authors.forename: Jasmine
authors.initials: J
authors.lastname: Chukwueke
authors.affiliation: Department of Pathology, Rhode Island Hospital, USA.
authors.forename: John E
authors.initials: JE
authors.lastname: Donahue
authors.affiliation: Department of Neurosurgery, Warren Alpert Medical School of Brown University, USA.
authors.forename: Conrad E
authors.initials: CE
authors.lastname: Johanson
authors.affiliation: Department of Surgery, University of California San Diego School of Medicine, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Baird
authors.affiliation: Department of Pathology, Rhode Island Hospital, USA; Department of Neurosurgery, Warren Alpert Medical School of Brown University, USA.
authors.forename: Edward G
authors.initials: EG
authors.lastname: Stopa
keywords: Alzheimer’s disease; Ecrg4; Neurofibrillary tangle; Neuroimmune mechanisms; White matter