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Converging Pathways of Chromogranin and Amyloid Metabolism in the Brain

Mattsson, Niklas ; Johansson, Per LU ; Hansson, Oskar LU orcid ; 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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organization
publishing date
type
Contribution to journal
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
project
Endocrine and diagnostic aspects of cognitive impairment
language
English
LU publication?
yes
id
7fcbd33a-b336-4130-b83c-0ac011e2d1b6 (old id 1657905)
date added to LUP
2016-04-01 09:52:41
date last changed
2022-04-27 08:24:22
@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}},
  keywords     = {{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}},
  doi          = {{10.3233/JAD-2010-091651}},
  volume       = {{20}},
  year         = {{2010}},
}