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Converging Pathways of Chromogranin and Amyloid Metabolism in the Brain

Mattsson, Niklas; Johansson, Per LU ; Hansson, Oskar LU ; Wallin, Anders; Johansson, Jan-Ove; Andreasson, Ulf; Andersen, Oluf; Haghighi, Sara; Olsson, Maria and Stridsberg, Mats, et al. (2010) In Journal of Alzheimer's Disease 20(4). p.1039-1048
Abstract
Much is unknown regarding the regulation of Alzheimer-related amyloid-beta protein precursor (A beta PP)-processing in the human central nervous system. It has been hypothesized that amyloidogenic A beta PP-processing preferentially occurs in the regulated secretory pathway of neurons. To test this hypothesis we looked for correlations of A beta PP-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 A beta(1-42), A beta(x-42), A beta(x-40), A beta(x-38), alpha-cleaved soluble A beta PP (sA beta PP... (More)
Much is unknown regarding the regulation of Alzheimer-related amyloid-beta protein precursor (A beta PP)-processing in the human central nervous system. It has been hypothesized that amyloidogenic A beta PP-processing preferentially occurs in the regulated secretory pathway of neurons. To test this hypothesis we looked for correlations of A beta PP-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 A beta(1-42), A beta(x-42), A beta(x-40), A beta(x-38), alpha-cleaved soluble A beta PP (sA beta PP alpha), beta-cleaved soluble A beta PP (sA beta PP beta), and peptides derived from CgB and SgII (Secretogranin-II, CgC). We investigated CSF levels of the protease BACE1, which processes A beta PP into A beta, 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 sA beta PP and A beta 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 A beta PP in the human central nervous system is processed in the regulated secretory pathway of neurons. (Less)
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publication status
published
subject
keywords
metabolism, chromogranin, Amyloid, BACE1, regulated secretory pathway
in
Journal of Alzheimer's Disease
volume
20
issue
4
pages
1039 - 1048
publisher
IOS Press
external identifiers
  • wos:000279539500010
  • scopus:77954552786
ISSN
1387-2877
DOI
10.3233/JAD-2010-091651
language
English
LU publication?
yes
id
7fcbd33a-b336-4130-b83c-0ac011e2d1b6 (old id 1657905)
date added to LUP
2010-08-24 13:17:40
date last changed
2018-05-29 10:41:13
@article{7fcbd33a-b336-4130-b83c-0ac011e2d1b6,
  abstract     = {Much is unknown regarding the regulation of Alzheimer-related amyloid-beta protein precursor (A beta PP)-processing in the human central nervous system. It has been hypothesized that amyloidogenic A beta PP-processing preferentially occurs in the regulated secretory pathway of neurons. To test this hypothesis we looked for correlations of A beta PP-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 A beta(1-42), A beta(x-42), A beta(x-40), A beta(x-38), alpha-cleaved soluble A beta PP (sA beta PP alpha), beta-cleaved soluble A beta PP (sA beta PP beta), and peptides derived from CgB and SgII (Secretogranin-II, CgC). We investigated CSF levels of the protease BACE1, which processes A beta PP into A beta, 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 sA beta PP and A beta 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 A beta PP in the human central nervous system is processed in the regulated secretory pathway of neurons.},
  author       = {Mattsson, Niklas and Johansson, Per and Hansson, Oskar and Wallin, Anders and Johansson, Jan-Ove and Andreasson, Ulf and Andersen, Oluf and Haghighi, Sara and Olsson, Maria and Stridsberg, Mats and Svensson, Johan and Blennow, Kaj and Zetterberg, Henrik},
  issn         = {1387-2877},
  keyword      = {metabolism,chromogranin,Amyloid,BACE1,regulated secretory pathway},
  language     = {eng},
  number       = {4},
  pages        = {1039--1048},
  publisher    = {IOS Press},
  series       = {Journal of Alzheimer's Disease},
  title        = {Converging Pathways of Chromogranin and Amyloid Metabolism in the Brain},
  url          = {http://dx.doi.org/10.3233/JAD-2010-091651},
  volume       = {20},
  year         = {2010},
}