Multiplex proteomics identifies novel CSF and plasma biomarkers of early Alzheimer's disease.
Acta Neuropathol Commun
; 7(1): 169, 2019 11 06.
Article
em En
| MEDLINE
| ID: mdl-31694701
ABSTRACT
To date, the development of disease-modifying therapies for Alzheimer's disease (AD) has largely focused on the removal of amyloid beta Aß fragments from the CNS. Proteomic profiling of patient fluids may help identify novel therapeutic targets and biomarkers associated with AD pathology. Here, we applied the Olink™ ProSeek immunoassay to measure 270 CSF and plasma proteins across 415 Aß- negative cognitively normal individuals (Aß- CN), 142 Aß-positive CN (Aß+ CN), 50 Aß- mild cognitive impairment (MCI) patients, 75 Aß+ MCI patients, and 161 Aß+ AD patients from the Swedish BioFINDER study. A validation cohort included 59 Aß- CN, 23 Aß- + CN, 44 Aß- MCI and 53 Aß+ MCI. To compare protein concentrations in patients versus controls, we applied multiple linear regressions adjusting for age, gender, medications, smoking and mean subject-level protein concentration, and corrected findings for false discovery rate (FDR, q < 0.05). We identified, and replicated, altered levels of ten CSF proteins in Aß+ individuals, including CHIT1, SMOC2, MMP-10, LDLR, CD200, EIF4EBP1, ALCAM, RGMB, tPA and STAMBP (- 0.14 < d < 1.16; q < 0.05). We also identified and replicated alterations of six plasma proteins in Aß+ individuals OSM, MMP-9, HAGH, CD200, AXIN1, and uPA (- 0.77 < d < 1.28; q < 0.05). Multiple analytes associated with cognitive performance and cortical thickness (q < 0.05). Plasma biomarkers could distinguish AD dementia (AUC = 0.94, 95% CI = 0.87-0.98) and prodromal AD (AUC = 0.78, 95% CI = 0.68-0.87) from CN. These findings reemphasize the contributions of immune markers, phospholipids, angiogenic proteins and other biomarkers downstream of, and potentially orthogonal to, Aß- and tau in AD, and identify candidate biomarkers for earlier detection of neurodegeneration.
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Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Proteômica
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Doença de Alzheimer
Tipo de estudo:
Diagnostic_studies
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Etiology_studies
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Incidence_studies
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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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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Acta Neuropathol Commun
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos