Expression of ErbB4 in the neurons of Alzheimer's disease brain and APP/PS1 mice, a model of Alzheimer's disease

Woo, Ran-Sook; Lee, Ji Hye; Yu, Ha Nul; Song, Dae-Yong; Baik, Tai-Kyoung

doi:10.5115/acb.2011.44.2.116

Cited by 45 publications

(43 citation statements)

References 53 publications

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“…Thus, altered levels of ERBB4 result in abnormalities that are consistent with features seen in several mouse models of DS, including the Tc1. Levels of ERBB4 are also elevated in brains from patients with AD, particularly in hippocampal and basal forebrain neurons, and similar increases are seen in the hippocampus and cortex from the APP/PSEN1 double-transgenic mouse model of AD (40). As in the Tc1 mice, it is not known whether these increases in ERBB4 protein levels contribute to, or are a consequence of, the disease process, but analysis of ERBB4 expression in DS and in AD in DS is warranted.…”

Section: Discussionmentioning

confidence: 78%

Protein profiles in Tc1 mice implicate novel pathway perturbations in the Down syndrome brain

Ahmed¹,

Dhanasekaran²,

Tong

et al. 2013

Human Molecular Genetics

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Tc1 mouse model of Down syndrome (DS) is functionally trisomic for ∼120 human chromosome 21 (HSA21) classical protein-coding genes. Tc1 mice display features relevant to the DS phenotype, including abnormalities in learning and memory and synaptic plasticity. To determine the molecular basis for the phenotypic features, the levels of 90 phosphorylation-specific and phosphorylation-independent proteins were measured by Reverse Phase Protein Arrays in hippocampus and cortex, and 64 in cerebellum, of Tc1 mice and littermate controls. Abnormal levels of proteins involved in MAP kinase, mTOR, GSK3B and neuregulin signaling were identified in trisomic mice. In addition, altered correlations among the levels of N-methyl-D-aspartate (NMDA) receptor subunits and the HSA21 proteins amyloid beta (A4) precursor protein (APP) and TIAM1, and between immediate early gene (IEG) proteins and the HSA21 protein superoxide dismutase-1 (SOD1) were found in the hippocampus of Tc1 mice, suggesting altered stoichiometry among these sets of functionally interacting proteins. Protein abnormalities in Tc1 mice were compared with the results of a similar analysis of Ts65Dn mice, a DS mouse model that is trisomic for orthologs of 50 genes trisomic in the Tc1 plus an additional 38 HSA21 orthologs. While there are similarities, abnormalities unique to the Tc1 include increased levels of the S100B calcium-binding protein, mTOR proteins RAPTOR and P70S6, the AMP-kinase catalytic subunit AMPKA, the IEG proteins FBJ murine osteosarcoma viral oncogene homolog (CFOS) and activity-regulated cytoskeleton-associated protein (ARC), and the neuregulin 1 receptor ERBB4. These data identify novel perturbations, relevant to neurological function and to some seen in Alzheimer's disease, that may occur in the DS brain, potentially contributing to phenotypic features and influencing drug responses.

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Section: Discussionmentioning

confidence: 78%

Protein profiles in Tc1 mice implicate novel pathway perturbations in the Down syndrome brain

Ahmed¹,

Dhanasekaran²,

Tong

et al. 2013

Human Molecular Genetics

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“…A significant increase in ErbB4 immunoreactivity was also observed in AD human brains, and this was demonstrated to colocalize with the apoptotic signal Bax in apoptotic hippocampal pyramidal neurons, suggesting the possible role of NRG1/ErbB4 signaling as a survival signal in AD progression [67]. The authors in a more recent study showed that the immunoreactivities of ErbB4 and phospho-ErbB4 were of higher intensity in the neurons of the CA1-2 transitional field of AD brains compared to age-matched controls [68]. They also observed an increased ErbB4 expression in the neurons of the cortico medial nucleus amygdala, human basal forebrain and superior frontal gyrus of AD brains.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Copy Number Variation in Alzheimer’s Disease: The NIALOAD/ NCRAD Family Study

Swaminathan¹,

Shen²,

Kim³

et al. 2012

CAR

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Copy number variants (CNVs) are DNA regions that have gains (duplications) or losses (deletions) of genetic material. CNVs may encompass a single gene or multiple genes and can affect their function. They are hypothesized to play an important role in certain diseases. We previously examined the role of CNVs in late-onset Alzheimer's disease (AD) and mild cognitive impairment (MCI) using participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study and identified gene regions overlapped by CNVs only in cases (AD and/or MCI) but not in controls. Using a similar approach as ADNI, we investigated the role of CNVs using 794 AD and 196 neurologically evaluated control non-Hispanic Caucasian NIA-LOAD/NCRAD Family Study participants with DNA derived from blood/brain tissue. The controls had no family history of AD and were unrelated to AD participants. CNV calls were generated and analyzed after detailed quality review. 711 AD cases and 171 controls who passed all quality thresholds were included in case/control association analyses, focusing on candidate gene and genome-wide approaches. We identified genes overlapped by CNV calls only in AD cases but not controls. A trend for lower CNV call rate was observed for deletions as well as duplications in cases compared to controls. Gene-based association analyses confirmed previous findings in the ADNI study (ATXN1, HLA-DPB1, RELN, DOPEY2, GSTT1, CHRFAM7A, ERBB4, NRXN1) and identified a new gene (IMMP2L) that may play a role in AD susceptibility. Replication in independent samples as well as further analyses of these gene regions is warranted.

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“…The NRXN1 gene has been associated with autism [58], schizophrenia [59], and has been shown to have reduced expression with increasing AD severity [60]. The ERBB4 gene may play a possible role in the progression of AD pathology [61]–[63].…”

Section: Discussionmentioning

confidence: 99%

Analysis of Copy Number Variation in Alzheimer’s Disease in a Cohort of Clinically Characterized and Neuropathologically Verified Individuals

et al. 2012

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Copy number variations (CNVs) are genomic regions that have added (duplications) or deleted (deletions) genetic material. They may overlap genes affecting their function and have been shown to be associated with disease. We previously investigated the role of CNVs in late-onset Alzheimer's disease (AD) and mild cognitive impairment using Alzheimer’s Disease Neuroimaging Initiative (ADNI) and National Institute of Aging-Late Onset AD/National Cell Repository for AD (NIA-LOAD/NCRAD) Family Study participants, and identified a number of genes overlapped by CNV calls. To confirm the findings and identify other potential candidate regions, we analyzed array data from a unique cohort of 1617 Caucasian participants (1022 AD cases and 595 controls) who were clinically characterized and whose diagnosis was neuropathologically verified. All DNA samples were extracted from brain tissue. CNV calls were generated and subjected to quality control (QC). 728 cases and 438 controls who passed all QC measures were included in case/control association analyses including candidate gene and genome-wide approaches. Rates of deletions and duplications did not significantly differ between cases and controls. Case-control association identified a number of previously reported regions (CHRFAM7A, RELN and DOPEY2) as well as a new gene (HLA-DRA). Meta-analysis of CHRFAM7A indicated a significant association of the gene with AD and/or MCI risk (P = 0.006, odds ratio = 3.986 (95% confidence interval 1.490–10.667)). A novel APP gene duplication was observed in one case sample. Further investigation of the identified genes in independent and larger samples is warranted.

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Expression of ErbB4 in the neurons of Alzheimer's disease brain and APP/PS1 mice, a model of Alzheimer's disease

Cited by 45 publications

References 53 publications

Protein profiles in Tc1 mice implicate novel pathway perturbations in the Down syndrome brain

Protein profiles in Tc1 mice implicate novel pathway perturbations in the Down syndrome brain

Analysis of Copy Number Variation in Alzheimer’s Disease: The NIALOAD/ NCRAD Family Study

Analysis of Copy Number Variation in Alzheimer’s Disease in a Cohort of Clinically Characterized and Neuropathologically Verified Individuals

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