Tavares, EvaAntequera, DesireeLópez-González, IreneFerrer, IsidroMiñano, Francisco JCarro, Eva2023-01-252023-01-252016-08-04http://hdl.handle.net/10668/10345Increasing 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.enAgedAged, 80 and overAlzheimer DiseaseAnimalsAtrophyBrainCalcitonin Gene-Related PeptideCerebral CortexDisease Models, AnimalDisease ProgressionFemaleHippocampusHumansMaleMiceMice, Inbred C57BLMice, TransgenicMiddle AgedNeuronsUp-Regulationresearch article27497681open access10.1016/j.ajpath.2016.06.0061525-2191http://ajp.amjpathol.org/article/S0002944016302309/pdf