Convergence of chromogranin and amyloid metabolism in the brain.

Background: Much is unknown regarding the regulation of amyloid precursor protein (APP) processing in the human central nervous system. It has been hypothesized that amyloidogenic APP-processing preferentially occurs in the regulated secretory pathway of neurons. To test this hypothesis we looked for correlations of APP-derived molecules in CSF with chromogranin (Cg) derived peptides, representing the regulated secretion. Methods: 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 Aβ1-42, Aβx-42, Aβx-40, Aβx-38, α-cleaved soluble APP (α-sAPP), β-cleaved soluble APP (β-sAPP), and peptides derived from CgB and SgII (Secretogranin-II, CgC). We investigated CSF levels of the protease BACE1, which processes APP into Aβ, in relation to Cg-levels. Finally, we measured Cg levels in cell media from untreated and BACE1-inhibited SH-SY5Y human neuroblastoma cells. Results: CSF Cg levels correlated to sAPP and Aβ peptides in AD, MS and controls, and to CSF BACE1. Cell medium from BACE1-inhibited cells had decreased CgB levels. Conclusions: These results suggest that a large part of APP in the human central nervous system is processed in the regulated secretory pathway of neurons.

Mattsson, NiklasSahlgrenska Academy(Swepub:lu)med-nmn (author)
Hansson, OskarLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups(Swepub:lu)mphy-ohn (author)
Wallin, A. (author)
Johansson, J.-O. (author)
Andreasson, U. (author)
Andersen, O (author)
Haghighi, S. (author)
Olsson, M. (author)
Stridsberg, M (author)
Svensson, J. (author)
Blennow, K. (author)
Zetterberg, H. (author)
Skaraborg HospitalSahlgrenska Academy (creator_code:org_t)

By the author/editor: Johansson, Per; Mattsson, Niklas; Hansson, Oskar; Wallin, A.; Johansson, J.-O.; Andreasson, U.; show more...; Andersen, O; Haghighi, S.; Olsson, M.; Stridsberg, M; Svensson, J.; Blennow, K.; Zetterberg, H.; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Neurosciences

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