Cell adhesion molecules contribute to Alzheimer’s disease: multiple pathway analyses of two genome‐wide association studies

Liu, Guiyou; Jiang, Yixiang; Wang, Ping; Feng, Rennan; Jiang, Nan; Chen, Xiaoyun; Song, Hui; Chen, Zugen

doi:10.1111/j.1471-4159.2011.07547.x

Cited by 80 publications

(54 citation statements)

References 68 publications

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“…Previous Results from Pathway Analysis of AD GWAS Prior to this study, six pathway analyses of AD GWAS have been reported with five studies using the KEGG database [4][5][6][7][8][9]. We compared our findings with the previous pathway analyses of AD GWAS.…”

Section: Two Ad Brain Expression Gwas Datasetsmentioning

confidence: 97%

“…A large proportion of AD heritability has yet to be explained. Fortunately, the existing large-scale GWAS datasets provide strong support for the investigation of AD mechanisms using pathway analysis methods [4][5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

“…They observed significantly enriched pathways related to metabolism and the immune system [6]. We performed multiple pathway analyses of two publicly available AD GWAS datasets (French and Pfizer GWAS datasets) [7]. We identified cell adhesion molecules (CAM) as a consistent signal in AD.…”

Section: Introductionmentioning

confidence: 99%

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Integrating Genome-Wide Association Study and Brain Expression Data Highlights Cell Adhesion Molecules and Purine Metabolism in Alzheimer’s Disease

Zhang

Liao

et al. 2014

Mol Neurobiol

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Alzheimer's disease (AD) is the most common neurodegenerative disease in the elderly. Recently, genome-wide association studies (GWAS) have been used to investigate AD pathogenesis. However, a large proportion of AD heritability has yet to be explained. We previously identified the cell adhesion molecule (CAM) pathway as a consistent signal in two AD GWAS. However, it is unclear whether CAM is present in the Genetic and Environmental Risk for Alzheimer's Disease Consortium (GERAD) GWAS and brain expression GWAS. Meanwhile, we think integrating AD GWAS and AD brain expression datasets may provide complementary information to identify important pathways involved in AD. Here, we conducted a systems analysis using (1) KEGG pathways, (2) large-scale AD GWAS from GERAD (n = 11,789), (3) two brain expression GWAS datasets (n = 399) from the AD cerebellum and temporal cortex, and (4) previous results from pathway analysis of AD GWAS. Our results indicate that (1) CAM is a consistent signal in five AD GWAS; (2) CAM is the most significant signal in AD; (3) we confirmed previous AD risk pathways related to immune system and diseases, and cardiovascular disease, etc.; and (4) we highlighted the purine metabolism pathway in AD for the first time. We believe that our results may advance our understanding of AD mechanisms and will be very informative for future genetic studies in AD.

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Section: Two Ad Brain Expression Gwas Datasetsmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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Integrating Genome-Wide Association Study and Brain Expression Data Highlights Cell Adhesion Molecules and Purine Metabolism in Alzheimer’s Disease

Zhang

Liao

et al. 2014

Mol Neurobiol

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“…CAMs like N-cadherin (Reiss et al 2005), CD44 (Okamoto et al 2001;Stoeck et al 2006), L-selectin , and NCAM (neural cell adhesion molecule) (Kalus et al 2006), related to neuroinflammation, are confirmed to be substrates shedded by ADAM17. Although there is little direct evidence between EGF or CAM signaling and AD, by using GWAS (genome-wide association studies) datasets and Kyoto Encyclopaedia of Genes and Genomes (KEGG) analysis, there seemed to be potential relevance of CAM pathway to AD pathogenesis (Liu et al 2012) ( Table 2). Neutralization of the inflammation pathway, like TNFa signaling pathway, by blocking the interaction of the cytokine with its cognate receptors, has been demonstrated as a feasible approach to treating inflammatory disease.…”

Section: Adam17 and Ad-related Neuroinflammationmentioning

confidence: 99%

The Distinct Role of ADAM17 in APP Proteolysis and Microglial Activation Related to Alzheimer’s Disease

Meng

Wang

2015

Cell Mol Neurobiol

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Alzheimer's disease (AD) is a progressive neurodegenerative disease with the symptom of cognitive impairment. The deposition of amyloid β (Aβ) peptide is believed to be the primary cause to neuronal dystrophy and eventually dementia. Aβ is the proteolytic product from its precursor amyloid precursor protein (APP) by β- and γ- secretase. An optional cleavage by α-secretase happens inside the Aβ domain. ADAM17 is supposed to be the regulated α-secretase of APP. Enhanced activity of ADAM17 leads to the increasing secretion of neuroprotective soluble APP α fragment and reduction of Aβ generation, which may be benefit to the disease. ADAM17 is then considered the potential therapeutic target for AD. Microglia activation and neuroinflammation is another important event in AD pathogenesis. Interestingly, ADAM17 also participates in the cleavage of many other membrane-bound proteins, especially some inflammatory factors related to microglia activation. The facilitating role of ADAM17 in inflammation and further neuronal damage has also been illustrated. In results, the activation of ADAM17 as the solution to AD may be a tricky task. The comprehensive consideration and evaluation has to be carried out carefully before the final treatment. In the present review, the distinct role of ADAM17 in AD-related APP shedding and neuroinflammatory microglial activation will be carefully discussed.

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“…Basic and clinical research indicates that CAMs play an important role in mediation of the immune and inflammatory processes of cardiovascular diseases [25]. Genome-wide association studies also suggest that human diseases such as atherosclerosis and Alzheimer's disease are related to the processes of CAMs [26,27]. Intercellular adhesion molecule-1 (ICAM-1), as a member of the immunoglobulin superfamily, plays an important role in mediating leukocyte adhesion and the development of atherogenesis [28].…”

Section: Discussionmentioning

confidence: 99%

Identification of biomarkers for ischemic cardiomyopathy based on microarray data analysis

Yang

Huo

et al. 2017

Cardiol J.

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Cell adhesion molecules contribute to Alzheimer’s disease: multiple pathway analyses of two genome‐wide association studies

Cited by 80 publications

References 68 publications

Integrating Genome-Wide Association Study and Brain Expression Data Highlights Cell Adhesion Molecules and Purine Metabolism in Alzheimer’s Disease

Integrating Genome-Wide Association Study and Brain Expression Data Highlights Cell Adhesion Molecules and Purine Metabolism in Alzheimer’s Disease

The Distinct Role of ADAM17 in APP Proteolysis and Microglial Activation Related to Alzheimer’s Disease

Identification of biomarkers for ischemic cardiomyopathy based on microarray data analysis

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