Pharmacy Practice Faculty Publications

Title

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

Document Type

Article

Publication Date

10-1999

Journal Title

Neurobiology of Disease

ISSN

0969-9961

Volume

6

Issue

5

First Page

440

Last Page

449

DOI

http://dx.doi.org/10.1006/nbdi.1999.0268

PubMed ID

10527810

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.

Keywords

Amyloid beta-peptides, apoptosis, caspase 8, Alzheimer's disease, neurology