| First Author | Tavares E | Year | 2016 |
| Journal | Am J Pathol | Volume | 186 |
| Issue | 10 | Pages | 2723-35 |
| PubMed ID | 27497681 | Mgi Jnum | J:235609 |
| Mgi Id | MGI:5796889 | Doi | 10.1016/j.ajpath.2016.06.006 |
| Citation | Tavares E, et al. (2016) Potential Role of Aminoprocalcitonin in the Pathogenesis of Alzheimer Disease. Am J Pathol 186(10):2723-35 |
| abstractText | 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-beta (Abeta), 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 Abeta-related pathology. We found that NPCT is expressed in hippocampal and cortical neurons and Abeta-induced up-regulation of NPCT expression. Peripherally administered antibodies against NPCT decreased microglial activation, decreased circulating levels of proinflammatory cytokines, and prevented Abeta-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. |
