Amyloid beta protein toxicity mediated by the formation of amyloid-beta protein precursor complexes.
Ann Neurol
; 54(6): 781-9, 2003 Dec.
Article
em En
| MEDLINE
| ID: mdl-14681887
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.
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Base de dados:
MEDLINE
Assunto principal:
Precursor de Proteína beta-Amiloide
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article