Identification of preclinical Alzheimer's disease by a profile of pathogenic proteins in neurally derived blood exosomes: A case-control study.
Alzheimers Dement
; 11(6): 600-7.e1, 2015 Jun.
Article
em En
| MEDLINE
| ID: mdl-25130657
ABSTRACT
BACKGROUND:
Proteins pathogenic in Alzheimer's disease (AD) were extracted from neurally derived blood exosomes and quantified to develop biomarkers for the staging of sporadic AD.METHODS:
Blood exosomes obtained at one time-point from patients with AD (n = 57) or frontotemporal dementia (FTD) (n = 16), and at two time-points from others (n = 24) when cognitively normal and 1 to 10 years later when diagnosed with AD were enriched for neural sources by immunoabsorption. AD-pathogenic exosomal proteins were extracted and quantified by enzyme-linked immunosorbent assays.RESULTS:
Mean exosomal levels of total tau, P-T181-tau, P-S396-tau, and amyloid ß 1-42 (Aß1-42) for AD and levels of P-T181-tau and Aß1-42 for FTD were significantly higher than for case-controls. Step-wise discriminant modeling incorporated P-T181-tau, P-S396-tau, and Aß1-42 in AD, but only P-T181-tau in FTD. Classification of 96.4% of AD patients and 87.5% of FTD patients was correct. In 24 AD patients, exosomal levels of P-S396-tau, P-T181-tau, and Aß1-42 were significantly higher than for controls both 1 to 10 years before and when diagnosed with AD.CONCLUSIONS:
Levels of P-S396-tau, P-T181-tau, and Aß1-42 in extracts of neurally derived blood exosomes predict the development of AD up to 10 years before clinical onset.Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
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Peptídeos beta-Amiloides
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Proteínas tau
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Exossomos
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Demência Frontotemporal
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Doença de Alzheimer
Tipo de estudo:
Diagnostic_studies
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Observational_studies
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Prevalence_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Alzheimers Dement
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Estados Unidos