Sequence variants of IDE are associated with the extent of beta-amyloid deposition in the Alzheimer's disease brain.
Neurobiol Aging
; 26(6): 795-802, 2005 Jun.
Article
em En
| MEDLINE
| ID: mdl-15718037
ABSTRACT
Insulin degrading enzyme, encoded by IDE, plays a primary role in the degradation of amyloid beta-protein (A beta), the deposition of which in senile plaques is one of the defining hallmarks of Alzheimer's disease (AD). We recently identified haplotypes in a broad linkage disequilibrium (LD) block encompassing IDE that associate with several AD-related quantitative traits. Here, by examining 32 polymorphic markers extending across IDE and testing quantitative measures of plaque density and cognitive function in three independent Swedish AD samples, we have refined the probable position of pathogenic sequences to a 3' region of IDE, with local maximum effects in the proximity of marker rs1887922. To replicate these findings, a subset of variants were examined against measures of brain A beta load in an independent English AD sample, whereby maximum effects were again observed for rs1887922. For both Swedish and English autopsy materials, variation at rs1887922 explained approximately 10% of the total variance in the respective histopathology traits. However, across all clinical materials studied to date, this variant site does not appear to associate directly with disease, suggesting that IDE may affect AD severity rather than risk. Results indicate that alleles of IDE contribute to variability in A beta deposition in the AD brain and suggest that this relationship may have relevance for the degree of cognitive dysfunction in AD patients.
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Base de dados:
MEDLINE
Assunto principal:
Encéfalo
/
Peptídeos beta-Amiloides
/
Mapeamento Cromossômico
/
Doença de Alzheimer
/
Insulisina
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
País/Região como assunto:
Europa
Idioma:
En
Revista:
Neurobiol Aging
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Suécia