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Ann Neurol. 2003 Dec;54(6):781-9.

Amyloid beta protein toxicity mediated by the formation of amyloid-beta protein precursor complexes.

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1
Department of Neurosciences, University of California-San Diego, 9500 Gilman Drive, Mail Code 0691, La Jolla, CA 92093-0691, USA.

Abstract

The amyloid-beta protein precursor, a type 1 transmembrane protein, gives rise to the amyloid beta-protein, a neurotoxic peptide postulated to be involved in the pathogenesis of Alzheimer's disease. Here, we show that soluble amyloid beta protein accelerates amyloid precursor protein complex formation, a process that contributes to neuronal cell death. The mechanism of cell death involves the recruitment of caspase-8 to the complex, followed by intracytoplasmic caspase cleavage of amyloid precursor protein. In vivo, the levels of soluble amyloid beta protein correlated with caspase-cleaved fragments of the amyloid precursor protein in brains of Alzheimer's disease subjects. These findings suggest that soluble amyloid beta protein-induced multimerization of the amyloid precursor protein may be another mechanism by which amyloid beta protein contributes to synapse loss and neuronal cell death seen in Alzheimer's disease.

PMID:
14681887
DOI:
10.1002/ana.10761
[Indexed for MEDLINE]
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