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Converging Pathways of Chromogranin and Amyloid Metabolism in the Brain
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2010 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, Vol. 20, no 4, 1039-1049 p.Article in journal (Refereed) Published
Abstract [en]

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 Abeta{1-42}, Abeta{x-42}, Abeta{x-40}, Abeta{x-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.

Place, publisher, year, edition, pages
2010. Vol. 20, no 4, 1039-1049 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-124335DOI: 10.3233/JAD-2010-091651ISI: 000279539500010PubMedID: 20413871OAI: oai:DiVA.org:uu-124335DiVA: diva2:317357
Available from: 2010-05-03 Created: 2010-05-03 Last updated: 2011-01-03Bibliographically approved

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