Genetic Regulatory Network Analysis for<i>App</i>Based on Genetical Genomics Approach

Wang, Xusheng; Chen, Ying; Wang, Xiaodong; Lu, Lu

doi:10.1080/03610730903418729

Cited by 14 publications

(11 citation statements)

References 37 publications

(33 reference statements)

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“…A consequence of this breeding scheme is that the genetic background is comparable: predominantly C57Bl/6 with a variable contribution of 129Sv and 129Ola. Although it is known that genetic background can influence the AD phenotype (Wang et al, ), we did not detect a larger variation in plaque deposition or transcript levels between animals within one of the raised experimental groups compared with the AD and CTR‐C57Bl/6 inbred groups studied previously. For instance; the interindividual variance of the transcript levels in the experimental groups studied here was similar and resembled what was found in our previous study on AD and CTR‐C57Bl/6 (Kamphuis et al, ).…”

Section: Methodscontrasting

confidence: 83%

GFAP and vimentin deficiency alters gene expression in astrocytes and microglia in wild‐type mice and changes the transcriptional response of reactive glia in mouse model for Alzheimer's disease

Kamphuis

Kooijman

Orre

et al. 2015

Glia

128

105

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Reactive astrocytes with an increased expression of intermediate filament (IF) proteins Glial Fibrillary Acidic Protein (GFAP) and Vimentin (VIM) surround amyloid plaques in Alzheimer's disease (AD). The functional consequences of this upregulation are unclear. To identify molecular pathways coupled to IF regulation in reactive astrocytes, and to study the interaction with microglia, we examined WT and APPswe/PS1dE9 (AD) mice lacking either GFAP, or both VIM and GFAP, and determined the transcriptome of cortical astrocytes and microglia from 15- to 18-month-old mice. Genes involved in lysosomal degradation (including several cathepsins) and in inflammatory response (including Cxcl5, Tlr6, Tnf, Il1b) exhibited a higher AD-induced increase when GFAP, or VIM and GFAP, were absent. The expression of Aqp4 and Gja1 displayed the same pattern. The downregulation of neuronal support genes in astrocytes from AD mice was absent in GFAP/VIM null mice. In contrast, the absence of IFs did not affect the transcriptional alterations induced by AD in microglia, nor was the cortical plaque load altered. Visualizing astrocyte morphology in GFAP-eGFP mice showed no clear structural differences in GFAP/VIM null mice, but did show diminished interaction of astrocyte processes with plaques. Microglial proliferation increased similarly in all AD groups. In conclusion, absence of GFAP, or both GFAP and VIM, alters AD-induced changes in gene expression profile of astrocytes, showing a compensation of the decrease of neuronal support genes and a trend for a slightly higher inflammatory expression profile. However, this has no consequences for the development of plaque load, microglial proliferation, or microglial activation.

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Section: Methodscontrasting

confidence: 83%

GFAP and vimentin deficiency alters gene expression in astrocytes and microglia in wild‐type mice and changes the transcriptional response of reactive glia in mouse model for Alzheimer's disease

Kamphuis

Kooijman

Orre

et al. 2015

Glia

128

105

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show abstract

“…Ray et al identified 6 coexpressed gene modules, each of which represented a biological process perturbed in AD [5]. By combining array analysis and quantitative trait loci (QTL) mapping to characterize the genetic variation and genetic regulatory network, Wang et al identified many AD-related genes coregulating with App including Gsk3b, Falz, Mef2a, Tlk2, Rtn, and Prkca [6]. Zhang et al found regulators of tmem59 and reconstructed gene regulatory networks of mouse neural stem cells.…”

Section: Introductionmentioning

confidence: 99%

Dynamic Regulatory Network Reconstruction for Alzheimer’s Disease Based on Matrix Decomposition Techniques

Kong

Mou

Zhi

et al. 2014

Computational and Mathematical Methods in Medicine

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Alzheimer's disease (AD) is the most common form of dementia and leads to irreversible neurodegenerative damage of the brain. Finding the dynamic responses of genes, signaling proteins, transcription factor (TF) activities, and regulatory networks of the progressively deteriorative progress of AD would represent a significant advance in discovering the pathogenesis of AD. However, the high throughput technologies of measuring TF activities are not yet available on a genome-wide scale. In this study, based on DNA microarray gene expression data and a priori information of TFs, network component analysis (NCA) algorithm is applied to determining the TF activities and regulatory influences on TGs of incipient, moderate, and severe AD. Based on that, the dynamical gene regulatory networks of the deteriorative courses of AD were reconstructed. To select significant genes which are differentially expressed in different courses of AD, independent component analysis (ICA), which is better than the traditional clustering methods and can successfully group one gene in different meaningful biological processes, was used. The molecular biological analysis showed that the changes of TF activities and interactions of signaling proteins in mitosis, cell cycle, immune response, and inflammation play an important role in the deterioration of AD.

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“…PRKCA and TP53 appeared to be the start nodes of the top subnetworks identified in multiple runs. The PRKCA gene was previously reported as being associated with an altered amyloid precursor protein (APP) secretion in fibroblasts from AD patients [43, 44]. Culmsee et al demonstrated that TP53 was a novel gene as a biomarker of AD and was related to neurodegenerative processes [45].…”

Section: Resultsmentioning

confidence: 99%

Genome-wide network-based pathway analysis of CSF t-tau/Aβ1-42 ratio in the ADNI cohort

et al. 2017

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Background: The cerebrospinal fluid (CSF) levels of total tau (t-tau) and Aβ 1-42 are potential early diagnostic markers for probable Alzheimer's disease (AD). The influence of genetic variation on these CSF biomarkers has been investigated in candidate or genome-wide association studies (GWAS). However, the investigation of statistically modest associations in GWAS in the context of biological networks is still an under-explored topic in AD studies. The main objective of this study is to gain further biological insights via the integration of statistical gene associations in AD with physical protein interaction networks.

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Genetic Regulatory Network Analysis forAppBased on Genetical Genomics Approach

Cited by 14 publications

References 37 publications

GFAP and vimentin deficiency alters gene expression in astrocytes and microglia in wild‐type mice and changes the transcriptional response of reactive glia in mouse model for Alzheimer's disease

GFAP and vimentin deficiency alters gene expression in astrocytes and microglia in wild‐type mice and changes the transcriptional response of reactive glia in mouse model for Alzheimer's disease

Dynamic Regulatory Network Reconstruction for Alzheimer’s Disease Based on Matrix Decomposition Techniques

Genome-wide network-based pathway analysis of CSF t-tau/Aβ1-42 ratio in the ADNI cohort

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