Tavares, EvaAntequera, DesireeLópez González, IreneFerrer, Isidro (Ferrer Abizanda)Miñano, Francisco J.Carro, Eva2020-04-162020-04-162016-10-010002-9440https://hdl.handle.net/2445/155477Increasing 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-b (Ab), 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 Ab-related pathology. We found that NPCT is expressed in hippocampal and cortical neurons and Ab-induced up-regulation of NPCT expression. Peripherally administered antibodies against NPCT decreased microglial activation, decreased circulating levels of proinflammatory cytokines, and prevented Ab-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.13 p.application/pdfengcc-by-nc-nd (c) American Society for Investigative Pathology, 2016http://creativecommons.org/licenses/by-nc-nd/3.0/esMalaltia d'AlzheimerEtiologiaCalcitoninaMetabolismeAlzheimer's diseaseEtiologyCalcitoninMetabolisminfo:eu-repo/semantics/article6671972020-04-16info:eu-repo/semantics/openAccess27497681