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Front. Neurosci. | doi: 10.3389/fnins.2018.00864

Natriuretic Peptides in Post-mortem Brain Tissue and Cerebrospinal Fluid of Non-demented Humans and Alzheimer’s disease Patients

  • 1Feinberg School of Medicine, Northwestern University, United States
  • 2Leiden University Medical Center, Netherlands
  • 3Percuros B.V., Netherlands
  • 4Delft University of Technology, Netherlands
  • 5Institute for Clinical and Translational Research, School of Medicine, Johns Hopkins University, United States
  • 6Johns Hopkins University, United States

Animal studies suggest the involvement of natriuretic peptides (NP) in several brain functions that are known to be disturbed during Alzheimer’s disease (AD). However, it remains unclear whether such findings extend to humans. In this study, we aimed to: 1) map the gene expression and localization of NP and their receptors (NPR) in human post-mortem brain tissue; 2) compare the relative amounts of NP and NPR between the brain tissue of AD patients and non-demented controls and 3) compare the relative amounts of NP between the cerebrospinal fluid (CSF) of AD patients and non-demented controls. Using the publicly available Allen Human Brain Atlas dataset, we mapped the gene expression of NP and NPR in healthy humans. Using immunohistochemistry, we visualized the localization of NP and NPR in the frontal cortex of AD patients (n=10, mean age 85.8 ± 6.2 years) and non-demented controls (mean age = 80.2 ± 9.1 years). Using Western blotting and ELISA, we quantified the relative amounts of NP and NPR in the brain tissue and CSF of these AD patients and non-demented controls. Our results showed that NP and NPR genes were ubiquitously expressed throughout the brain in healthy humans. NP and NPR were present in various cellular structures including in neurons, astrocyte-like structures, and cerebral vessels in both AD patients and non-demented controls. Furthermore, we found higher amounts of NPR type-A in the brain of AD patients (p=0.045) and lower amounts of NP type-B in the CSF of AD patients (p=0.029). In conclusion, this study shows the abundance of NP and NPR in the brain of humans suggesting involvement of NP in various brain functions. In addition, our findings suggest alterations of NP levels in the brain of AD patients. The role of NP in the development and progression of AD remains to be elucidated.

Keywords: Natriuretic Peptides, Brain, Cerebrospinal Fluid, Alzheimer Disease, Humans, Gene Expression

Received: 24 Aug 2018; Accepted: 05 Nov 2018.

Edited by:

Laura Ferraiuolo, University of Sheffield, United Kingdom

Reviewed by:

Scott E. Counts, Michigan State University, United States
Yannick Vermeiren, University of Antwerp, Belgium  

Copyright: © 2018 Mahinrad, Bulk, van der Velpen, Mahfouz, van Roon-Mom, Fedarko, Yasar, Sabayan, Van Heemst and Van Der Weerd. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Simin Mahinrad, Feinberg School of Medicine, Northwestern University, Chicago, United States, simin.rad@northwestern.edu