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Multi-tissue gene expression profiles of human brain (PFC)

ABSTRACT: The genetics of complex disease produce alterations in molecular interactions of cellular pathways which collective effect may become clear through the organized structure of molecular networks. To characterize molecular systems associated with late-onset Alzheimer´s disease (LOAD), we constructed gene regulatory networks in hundreds of autopsied brain tissues from LOAD patients and non-demented subjects. We demonstrate that LOAD reconfigures specific portions of the molecular interaction structure, and via an integrative network-based approach we rank ordered these sub-networks (modules) for relevance to LOAD pathology, highlighting the immune/microglia module as the top ranking. Through a Bayesian inference approach we identified multiple key causal regulators for LOAD brains.

ORGANISM(S): Homo sapiens

PROVIDER: GSE44770 | GEO | 2013/04/25

SECONDARY ACCESSION(S): PRJNA191618

REPOSITORIES: GEO

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Multi-tissue gene expression profiles of human brain (PFC)

Project description:The genetics of complex disease produce alterations in molecular interactions of cellular pathways which collective effect may become clear through the organized structure of molecular networks. To characterize molecular systems associated with late-onset Alzheimer´s disease (LOAD), we constructed gene regulatory networks in hundreds of autopsied brain tissues from LOAD patients and non-demented subjects. We demonstrate that LOAD reconfigures specific portions of the molecular interaction structure, and via an integrative network-based approach we rank ordered these sub-networks (modules) for relevance to LOAD pathology, highlighting the immune/microglia module as the top ranking. Through a Bayesian inference approach we identified multiple key causal regulators for LOAD brains. Autopsied tissues from dorsolateral prefrontal cortex (PFC), visual cortex (VC) and cerebellum (CR) in brains of LOAD patients, and non-demented healthy controls, collected through the Harvard Brain Tissue Resource Center (HBTRC), were profiled on a custom-made Agilent 44K array (GPL4372_1). All subjects were diagnosed at intake and each brain underwent extensive LOAD-related pathology examination. Gene expression analyses were adjusted for age and sex, postmortem interval (PMI) in hours, sample pH and RNA integrity number (RIN). In the overall cohort of LOAD and non-demented brains the mean ± SD for sample PMI, pH and RIN were 17.8±8.3, 6.4±0.3 and 6.8±0.8, respectively. 230 samples with all PFC, VC, and CR tissue profiled were included for further multi-tissue analysis.

2013-04-25 | E-GEOD-44770 | biostudies-arrayexpress

Multi-tissue gene expression profiles of human brain (VC)

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Dementia Comparison: VaD vs. AD vs. Controls

Project description:Gene expression profiling was performed on frontal and temporal cortex from vascular dementia (VaD), Alzheimer's disease (AD), and non-demented controls (Control) obtained from the University of Michigan Brain Bank. Controls and AD cases had no infarcts in the autopsied hemisphere. Vascular dementia cases had low Braak staging.

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Project description:we explored the proteome of the area where they are located; the outer two-thirds of the molecular layer of the dentate gyrus. This area was microdissected from five subjects with Alzheimer disease and five non-demented controls, and quantitative mass spectrometry of pre-fractionated samples was performed.

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Project description:Late-onset Alzheimer disease (LOAD) is the most common neurodegenerative disorder worldwide. Recent studies have shown that differential expression in genes (DEG) related to inflammatory response may result associated with disease onset and progression. This study aimed to explore the molecular pathogenesis of LOAD-related inflammation through next-generation sequencing, to assess RNA expression profiles in Alzheimer's disease patients and healthy controls.

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