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Converging pathways of chromogranin and amyloid metabolism in the brain.

Journal article
Authors Niklas Mattsson
Per Johansson
Oskar Hansson
Anders Wallin
Jan-Ove Johansson
Ulf Andreasson
Oluf Andersen
Sara Haghighi
Maria Olsson
Mats Stridsberg
Johan Svensson
Kaj Blennow
Henrik Zetterberg
Published in Journal of Alzheimer's disease : JAD
Volume 20
Issue 4
Pages 1039-49
ISSN 1875-8908
Publication year 2010
Published at Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Institute of Medicine, Department of Internal Medicine
Pages 1039-49
Language en
Links dx.doi.org/10.3233/JAD-2010-091651
Subject categories Psychiatry

Abstract

Much is unknown regarding the regulation of Alzheimer-related amyloid-beta protein precursor (AbetaPP)-processing in the human central nervous system. It has been hypothesized that amyloidogenic AbetaPP-processing preferentially occurs in the regulated secretory pathway of neurons. To test this hypothesis we looked for correlations of AbetaPP-derived molecules in cerebrospinal fluid (CSF) with chromogranin (Cg) derived peptides, representing the regulated secretion. Patients with Alzheimer's disease (AD, N=32), multiple sclerosis (MS, N=50), and healthy controls (N= 70) were enrolled. CSF was analyzed for the amyloid peptides Abeta1-42, Abetax-42, Abetax-40, Abetax-38, alpha-cleaved soluble AbetaPP (sAbetaPPalpha), beta-cleaved soluble AbetaPP (sAbetaPPbeta), and peptides derived from CgB and SgII (Secretogranin-II, CgC). We investigated CSF levels of the protease BACE1, which processes AbetaPP into Abeta, in relation to Cg-levels. Finally, we measured Cg levels in cell media from untreated and BACE1-inhibited SH-SY5Y human neuroblastoma cells. CSF Cg levels correlated to sAbetaPP and Abeta peptides in AD, MS, and controls, and to CSF BACE1. Cell medium from BACE1-inhibited cells had decreased CgB levels. These results suggest that a large part of AbetaPP in the human central nervous system is processed in the regulated secretory pathway of neurons.

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