Toxicity mediated by soluble oligomers of β-amyloid(1-42) on cholinergic SN56.B5.G4 cells

Katrin Heinitz, Martin Beck, Reinhard Schliebs, J. Regino Perez-Polo

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    Abstract

    Alzheimer's disease (AD) is characterized by cholinergic dysfunction and progressive basal forebrain cell loss which has been assumed to be as a result of the extensive accumulation of β-amyloid (Aβ). In addition to Aβ fibrillar assemblies, there are pre-fibrillar forms that have been shown to be neurotoxic, although their role in cholinergic degeneration is still not known. Using the cholinergic cell line SN56.B5.G4, we investigated the effect of different Aβ(1-42) aggregates on cell viability. In our model, only soluble oligomeric but not fibrillar Aβ(1-42) forms induced toxicity in cholinergic cells. To determine whether the neurotoxicity of oligomeric Aβ(1-42) was caused by its oxidative potential, we performed microarray analysis of SN56.B5.G4 cells treated either with oligomeric Aβ(1-42) or H2O2. We showed that genes affected by Aβ(1-42) differed from those affected by non-specific oxidative stress. Many of the genes affected by Aβ(1-42) were present in the endoplasmic reticulum (ER), Golgi apparatus and/or otherwise involved in protein modification and degradation (chaperones, ATF6), indicating a possible role for ER-mediated stress in Aβ-mediated toxicity. Moreover, a number of genes, which are known to be involved in AD (clusterin, Slc18a3), were identified. This study provides important leads for the understanding of oligomeric Aβ(1-42) toxicity in cholinergic cells, which may account in part for cholinergic degeneration in AD.

    Original languageEnglish (US)
    Pages (from-to)1930-1945
    Number of pages16
    JournalJournal of neurochemistry
    Volume98
    Issue number6
    DOIs
    StatePublished - Sep 1 2006

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    Keywords

    • Alzheimer's disease
    • Microarray
    • Oxidative stress
    • SN56.B5.G4 cells
    • β-amyloid

    ASJC Scopus subject areas

    • Biochemistry
    • Cellular and Molecular Neuroscience

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