title: Potential Role of Aminoprocalcitonin in the Pathogenesis of Alzheimer Disease.
abstract: Increasing evidence suggests that inflammatory responses cause brain atrophy and play a prominent and early role in the progression of Alzheimer disease. Recent findings show that the neuroendocrine peptide aminoprocalcitonin (NPCT) plays a critical role in the development of systemic inflammatory response; however, the presence, possible function, regulation, and mechanisms by which NPCT may be involved in Alzheimer disease neuropathology remain unknown. We explored the expression of NPCT and its interaction with amyloid-β (Aβ), and proinflammatory and neurogenic effects. By using brain samples of Alzheimer disease patients and APP/PS1 transgenic mice, we evaluated the potential role of NPCT on Aβ-related pathology. We found that NPCT is expressed in hippocampal and cortical neurons and Aβ-induced up-regulation of NPCT expression. Peripherally administered antibodies against NPCT decreased microglial activation, decreased circulating levels of proinflammatory cytokines, and prevented Aβ-induced neurotoxicity in experimental models of Alzheimer disease. Remarkably, anti-NPTC therapy resulted in a significant improvement in the behavioral status of APP/PS1 mice. Our results indicate a central role of NPCT in Alzheimer disease pathogenesis and suggest NPCT as a potential biomarker and therapeutic target.
authors: Clinical and Experimental Pharmacology Research Unit, Valme University Hospital, Seville, Spain. Electronic address: eva.tavares.exts@juntadeandalucia.es.
authors: Eva
authors: E
authors: Tavares
authors: Group of Neurodegenerative Diseases, Instituto de Investigacion Hospital 12 de Octubre (i+12), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Neurodegenerative Diseases Biomedical Research Center (CIBERNED), Madrid, Spain.
authors: Desiree
authors: D
authors: Antequera
authors: Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Neurodegenerative Diseases Biomedical Research Center (CIBERNED), Madrid, Spain; Institut de Neuropatologia, IDIBELL-Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Hospitalet de Llobregat, Spain; Universitat de Barcelona, Hospitalet de Llobregat, Barcelona, Spain.
authors: Irene
authors: I
authors: López-González
authors: Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Neurodegenerative Diseases Biomedical Research Center (CIBERNED), Madrid, Spain; Institut de Neuropatologia, IDIBELL-Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Hospitalet de Llobregat, Spain; Universitat de Barcelona, Hospitalet de Llobregat, Barcelona, Spain.
authors: Isidro
authors: I
authors: Ferrer
authors: Clinical and Experimental Pharmacology Research Unit, Valme University Hospital, Seville, Spain; Department of Pharmacology, Pediatrics and Radiology, Faculty of Medicine, University of Seville, Seville, Spain.
authors: Francisco J
authors: FJ
authors: Miñano
authors: Group of Neurodegenerative Diseases, Instituto de Investigacion Hospital 12 de Octubre (i+12), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Neurodegenerative Diseases Biomedical Research Center (CIBERNED), Madrid, Spain. Electronic address: carroeva@h12o.es.
authors: Eva
authors: E
authors: Carro
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D000818:Animals; D001284:Atrophy; D001921:Brain / Q000378:metabolism / Q000473:pathology; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation
chemical_list: C000606589:CALCA protein, human; C000606590:Calca protein, mouse; D015740:Calcitonin Gene-Related Peptide