Transcriptomics,Genomics

Dataset Information

57

Progressive modulation of the human olfactory bulb transcriptome during Alzheimer's disease evolution: novel insights into the olfactory signaling across proteinopathies


ABSTRACT: Alzheimer's disease (AD) is characterized by progressive dementia, initially presenting olfactory dysfunction. Despite the olfactory bulb (OB) is the first central structure of the olfactory pathway, we lack a complete molecular characterization of the transcriptional events that occurs in this olfactory area during AD progression. To address this gap in knowledge, we have assessed the genome-wide expression in postmortem OBs from subjects with varying degree of AD pathology. A stage-dependent deregulation of specific pathways was observed, revealing transmembrane transport, and neuroinflammation as part of the functional modules that are disrupted across AD grading. Potential drivers of neurodegeneration predicted by network-driven transcriptomics were monitored across different types of dementia, including progressive supranuclear palsy (PSP), mixed dementia, and frontotemporal lobar degeneration (FTLD). Epidermal growth factor receptor (EGFR) expression was significantly increased in the OB of AD and mixed dementia subjects. Moreover, a significant increment in the activation of signal transducer and activator of transcription 3 (STAT3) was exclusively detected in advanced AD stages, whereas total OB STAT3 levels were specifically overexpressed in mixed dementia. Furthermore, transcription factors deregulated in the OB of mixed dementia subjects such as cAMP Responsive Element Binding Protein 1 (CREB1) and AP-1 Transcription Factor Subunit (c-Jun) were not differentially modulated at olfactory level across AD grading. On the other hand, olfactory expression of this signal transducer panel were unchanged in PSP and FTLD subjects. Taken together, this study unveils cross-disease similarities and differences for specific signal transducers, providing new avenues of research into the role of olfactory signaling across proteinopathies. Overall design: 4 controls, 5 Alzheimer's disease (initial stage), 4 Alzheimer's disease (intermediate stage), 5 Alzheimer's disease (advanced stages).

INSTRUMENT(S): [HuGene-2_0-st] Affymetrix Human Gene 2.0 ST Array [transcript (gene) version]

SUBMITTER: Enrique Santamaría  

PROVIDER: GSE93885 | GEO | 2017-11-01

SECONDARY ACCESSION(S): PRJNA362662

REPOSITORIES: GEO

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Publications

Progressive modulation of the human olfactory bulb transcriptome during Alzheimer´s disease evolution: novel insights into the olfactory signaling across proteinopathies.

Lachen-Montes Mercedes M   Zelaya María Victoria MV   Segura Víctor V   Fernández-Irigoyen Joaquín J   Santamaría Enrique E  

Oncotarget 20170523 41


Alzheimer´s disease (AD) is characterized by progressive dementia, initially presenting olfactory dysfunction. Despite the olfactory bulb (OB) is the first central structure of the olfactory pathway, we lack a complete molecular characterization of the transcriptional events that occurs in this olfactory area during AD progression. To address this gap in knowledge, we have assessed the genome-wide expression in postmortem OBs from subjects with varying degree of AD pathology. A stage-dependent d  ...[more]

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