Elsevier

Neurobiology of Disease

Volume 6, Issue 5, October 1999, Pages 440-449
Neurobiology of Disease

Regular Article
Neuronal Apoptosis Induced by β-Amyloid Is Mediated by Caspase-8

https://doi.org/10.1006/nbdi.1999.0268Get rights and content

Abstract

The Alzheimer disease-associated β-amyloid peptide has been shown to induce apoptotic neuronal death. In the present study, we test the hypothesis that the apoptotic pathway activated by β-amyloid is similar to the pathway activated by the Fas/TNFR family of death receptors, which requires caspase-8 activity and adaptor proteins such as FADD. We demonstrate that the selective caspase-8 inhibitor IETD-fmk blocks neuronal death induced by β-amyloid. Furthermore, using viral-mediated gene delivery, we show that neurons expressing dominant-negative FADD are protected from apoptosis induced by β-amyloid. Together these results indicate that the apoptotic pathway activated by β-amyloid requires both caspase-8 activity and FADD. These findings further support the hypothesis that β-amyloid might initiate apoptosis by cross-linking death receptors of the Fas/TNFR family.

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    Abbreviations used: Aβ, Alzheimer's β-amyloid peptide; AD, Alzheimer's disease; APCD, activation-induced programmed cell death; Con A, concanavalin A; dnFADD, dominant-negative FADD; FasL, Fas ligand.

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