Network-driven plasma proteomics expose molecular changes in the Alzheimer's brain.
Mol Neurodegener
; 11: 31, 2016 04 26.
Article
de En
| MEDLINE
| ID: mdl-27112350
ABSTRACT
BACKGROUND:
Biological pathways that significantly contribute to sporadic Alzheimer's disease are largely unknown and cannot be observed directly. Cognitive symptoms appear only decades after the molecular disease onset, further complicating analyses. As a consequence, molecular research is often restricted to late-stage post-mortem studies of brain tissue. However, the disease process is expected to trigger numerous cellular signaling pathways and modulate the local and systemic environment, and resulting changes in secreted signaling molecules carry information about otherwise inaccessible pathological processes.RESULTS:
To access this information we probed relative levels of close to 600 secreted signaling proteins from patients' blood samples using antibody microarrays and mapped disease-specific molecular networks. Using these networks as seeds we then employed independent genome and transcriptome data sets to corroborate potential pathogenic pathways.CONCLUSIONS:
We identified Growth-Differentiation Factor (GDF) signaling as a novel Alzheimer's disease-relevant pathway supported by in vivo and in vitro follow-up experiments, demonstrating the existence of a highly informative link between cellular pathology and changes in circulatory signaling proteins.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Encéphale
/
Protéomique
/
Maladie d'Alzheimer
/
Réseau nerveux
Type d'étude:
Prognostic_studies
Limites:
Humans
Langue:
En
Journal:
Mol Neurodegener
Année:
2016
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique