Association of plasma clusterin concentration with severity, pathology, and progression in Alzheimer disease.
Arch Gen Psychiatry
; 67(7): 739-48, 2010 Jul.
Article
em En
| MEDLINE
| ID: mdl-20603455
ABSTRACT
CONTEXT Blood-based analytes may be indicators of pathological processes in Alzheimer disease (AD). OBJECTIVE:
To identify plasma proteins associated with AD pathology using a combined proteomic and neuroimaging approach.DESIGN:
Discovery-phase proteomics to identify plasma proteins associated with correlates of AD pathology. Confirmation and validation using immunodetection in a replication set and an animal model.SETTING:
A multicenter European study (AddNeuroMed) and the Baltimore Longitudinal Study of Aging.PARTICIPANTS:
Patients with AD, subjects with mild cognitive impairment, and healthy controls with standardized clinical assessments and structural neuroimaging. MAIN OUTCOMEMEASURES:
Association of plasma proteins with brain atrophy, disease severity, and rate of clinical progression. Extension studies in humans and transgenic mice tested the association between plasma proteins and brain amyloid.RESULTS:
Clusterin/apolipoprotein J was associated with atrophy of the entorhinal cortex, baseline disease severity, and rapid clinical progression in AD. Increased plasma concentration of clusterin was predictive of greater fibrillar amyloid-beta burden in the medial temporal lobe. Subjects with AD had increased clusterin messenger RNA in blood, but there was no effect of single-nucleotide polymorphisms in the gene encoding clusterin with gene or protein expression. APP/PS1 transgenic mice showed increased plasma clusterin, age-dependent increase in brain clusterin, as well as amyloid and clusterin colocalization in plaques.CONCLUSIONS:
These results demonstrate an important role of clusterin in the pathogenesis of AD and suggest that alterations in amyloid chaperone proteins may be a biologically relevant peripheral signature of AD.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Clusterina
/
Doença de Alzheimer
Tipo de estudo:
Clinical_trials
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Aged
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Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Arch Gen Psychiatry
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Reino Unido