title: The antimicrobial protein, CAP37, is upregulated in pyramidal neurons during Alzheimer's disease.
abstract: Inflammation is a well-defined factor in Alzheimer's disease (AD). There is a strong need to identify the molecules contributing to neuroinflammation so that therapies can be designed to prevent immune-mediated neurotoxicity. The cationic antimicrobial protein of 37 kDa (CAP37) is an inflammatory mediator constitutively expressed in neutrophils (PMNs). In addition to antibiotic activity, CAP37 exerts immunomodulatory effects on microglia. We hypothesize that CAP37 mediates the neuroinflammation associated with AD. However, PMNs are not customarily associated with the pathology of AD. This study was therefore designed to identify non-neutrophilic source(s) of CAP37 in brains of AD patients. Brain tissues from patients and age-matched controls were analyzed for CAP37 expression using immunohistochemistry (IHC). To determine factors that induce CAP37 in AD, HCN-1A primary human neurons were treated with tumor necrosis factor-alpha (TNF-α) or amyloid β1-40 (Aβ) and analyzed by IHC. Western blotting and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to confirm CAP37 expression in neurons and brain tissues. IHC revealed CAP37 in cortical neurons in temporal and parietal lobes as well as CA3 and CA4 hippocampal neurons in patients with AD. CAP37 was found in more neurons in AD patients compared with age-matched controls. qRT-PCR and Western blotting showed an increase in CAP37 transcript and protein in the AD temporal lobe, a brain region that is highly impacted in AD. qRT-PCR observations confirmed CAP37 expression in neurons. TNF-α and Aβ increased neuronal expression of CAP37. These findings support our hypothesis that neuronal CAP37 may modulate the neuroinflammatory response in AD.
authors.affiliation: Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, 1110 N. Stonewall Ave., CPB 255, Oklahoma City, OK, 73117, USA.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Brock
authors.affiliation: Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, 1110 N. Stonewall Ave., CPB 255, Oklahoma City, OK, 73117, USA.|Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, 1110 N. Stonewall Ave., CPB 255, Oklahoma City, OK, 73117, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Kasus-Jacobi
authors.affiliation: Department of Surgery, University of Oklahoma Health Sciences Center, 1122 NE 13th St., ORB 350, Oklahoma City, OK, 73117, USA.
authors.forename: Megan
authors.initials: M
authors.lastname: Lerner
authors.affiliation: Department of Geriatrics, University of Oklahoma Health Sciences Center, 975 NE 10th St., BRC 1303, Oklahoma City, OK, 73104, USA.
authors.forename: Sreemathi
authors.initials: S
authors.lastname: Logan
authors.affiliation: Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Rm 286A, Houston, TX, 77030, USA.
authors.forename: Adekunle M
authors.initials: AM
authors.lastname: Adesina
authors.affiliation: Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, 1110 N. Stonewall Ave., CPB 255, Oklahoma City, OK, 73117, USA. Anne-Pereira@ouhsc.edu.|Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, 1110 N. Stonewall Ave., CPB 255, Oklahoma City, OK, 73117, USA. Anne-Pereira@ouhsc.edu.|Department of Cell Biology, University of Oklahoma Health Sciences Center, 1110 N. Stonewall Ave., CPB 329, Oklahoma City, OK, USA. Anne-Pereira@ouhsc.edu.|Department of Pathology, University of Oklahoma Health Sciences Center, 1110 N. Stonewall Ave., CPB 329, Oklahoma City, OK, 73117, USA. Anne-Pereira@ouhsc.edu.
authors.forename: H
authors.initials: H
authors.lastname: Anne Pereira
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism*; D001798:Blood Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D002478:Cells, Cultured; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D010296:Parietal Lobe / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000494:pharmacology; D061251:Primary Cell Culture; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D013702:Temporal Lobe / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation; D055815:Young Adult
chemical_list: C062991:AZU1 protein, human; D016229:Amyloid beta-Peptides; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D002352:Carrier Proteins; D018836:Inflammation Mediators; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C078592:amyloid beta-protein (1-40)
keywords: Alzheimer’s disease; Amyloid-beta; CAP37; Microglia; Neuroinflammation; Neurons