Dissociation of ß-amyloid from lipoprotein in cerebrospinal fluid from Alzheimer's disease accelerates ß-amyloid-42 assembly.
J Neurosci Res
; 89(6): 815-21, 2011 Jun.
Article
em En
| MEDLINE
| ID: mdl-21394760
Monoclonal 2C3 specific to ß-amyloid (Aß) oligomers (AßOs) enabled us to test our hypothesis that the alteration of lipoprotein-Aß interaction in the central nervous system (CNS) initiates and/or accelerates the cascade favoring Aß assembly. Immunoprecipitation of frontal cortex employing 2C3 unequivocally detected soluble 4-, 8-, and 12-mers in Alzheimer's disease (AD) brains. Immunoblot analysis of the entorhinal cortex employing 2C3 revealed that the accumulation of soluble 12-mers precedes the appearance of neuronal loss or cognitive impairment and is enhanced as the Braak neurofibrially tangle (NFT) stages progress. The dissociation of soluble Aß from lipoprotein particles occurs in cerebrospinal fluid (CSF), and the presence of lipoprotein-free oligomeric 2C3 conformers (4- to 35-mers) was evident, which mimic CNS environments. Such CNS environments may strongly affect conformation of soluble Aß peptides, resulting in the conversion of soluble Aß(42) monomers into soluble Aß(42) assembly. The findings suggest that functionally declined lipoproteins may accelerate the generation of metabolic conditions leading to higher levels of soluble Aß(42) assembly in the CNS.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
/
Encéfalo
/
Peptídeos beta-Amiloides
/
Doença de Alzheimer
/
Lipoproteínas
Tipo de estudo:
Observational_studies
Limite:
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article