Aβ1-42 induces mild endoplasmic reticulum stress in an aggregation state-dependent manner

S.M. Chafekar, J.J.M. Hoozemans, R. Zwart, F. Baas, W. Scheper

Research output: Contribution to JournalArticleAcademicpeer-review


Alzheimer's disease (AD) is characterized by the aggregation of misfolded proteins. Previously we reported activation of the unfolded protein response (UPR) in AD neurons. A potential source for UPR activation in AD neurons may be the increased levels of β-amyloid (Aβ). In this study, we used preparations enriched in oligomeric or fibrillar Aβ1-42 to investigate the role of the conformational state of Aβ in UPR activation in differentiated neuroblastoma cells. Both oligomeric and fibrillar Aβ1-42 do not induce BiP expression to the extent that it can be detected in a pool of cells. However, using a fluorescent UPR reporter cell line that allows analysis of individual cells, we demonstrated mild activation of the UPR by oligomeric but not fibrillar Aβ1-42. We showed that oligomeric Aβ1-42 is significantly more toxic to cells primed for UPR than is fibrillar Aβ1-42, indicating that activation of the UPR contributes to oligomer-specific Aβ1-42 toxicity. Because UPR activation is observed in AD brain at a stage that precedes the massive fibrillar Aβ deposition and tangle formation, this may indicate a role for nonfibrillar Aβ in the induction of the UPR in AD neurons. © 2007 Mary Ann Liebert, Inc.
Original languageEnglish
Pages (from-to)2245-2254
JournalAntioxidants and Redox Signaling
Issue number12
Publication statusPublished - 1 Oct 2007
Externally publishedYes


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