Cell adhesion molecule pathway genes are regulated by cis-regulatory SNPs and show significantly altered expression in Alzheimer's disease brains

Bao, Xinjie; Liu, Gengfeng; Jiang, Yixiang; Jiang, Qinghua; Liao, Mingzhi; Feng, Rennan; Zhang, Liangcai; Ma, Guoda; Zhang, Shuyan; Chen, Zugen; Zhao, Bin; Wang, Renzhi; Li, Keshen; Liu, Guiyou

doi:10.1016/j.neurobiolaging.2015.06.006

Cited by 39 publications

(23 citation statements)

References 32 publications

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“…To detect more AD genetic signals, several pathway analyses of GWAS datasets have been conducted [6-11]. Lambert et al identified significant immune KEGG pathways and GO categories in AD [6].…”

Section: Introductionmentioning

confidence: 99%

Gene expression analysis reveals the dysregulation of immune and metabolic pathways in Alzheimer's disease

et al. 2016

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In recent years, several pathway analyses of genome-wide association studies reported the involvement of metabolic and immune pathways in Alzheimer's disease (AD). Until now, the exact mechanisms of these pathways in AD are still unclear. Here, we conducted a pathway analysis of a whole genome AD case-control expression dataset (n=41, 25 AD cases and 16 controls) from the human temporal cortex tissue. Using the differently expressed AD genes, we identified significant KEGG pathways related to metabolism and immune processes. Using the up- and down- regulated AD gene list, we further found up-regulated AD gene were significantly enriched in immune and metabolic pathways. We further compare the immune and metabolic KEGG pathways from the expression dataset with those from previous GWAS datasets, and found that most of these pathways are shared in both GWAS and expression datasets.

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Section: Introductionmentioning

confidence: 99%

Gene expression analysis reveals the dysregulation of immune and metabolic pathways in Alzheimer's disease

et al. 2016

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“…In fact, GWAS is an important first step to investigate the genetics of human complex diseases as widely described in previous studies 11 – 25 . In order to translate into opportunities for new diagnostics and therapies, we must identify the genes perturbed by these four variants, and understand how these variant functionally contributes to the underlying disease pathogenesis 3 – 8 , 12 , 26 – 30 . If a genetic variant is associated with increased or decreased expression of a particular gene, this suggests that the gene on which the variant acts could be in the causal pathway 31 .…”

Section: Discussionmentioning

confidence: 99%

“…Meanwhile, evidence shows that the effect of genetic variants on gene expression may occur in disease-relevant tissue types 3 – 9 . It is still necessary to investigate these potential expression associations in other human brain tissues, as Deckert et al .…”

Section: Introductionmentioning

confidence: 99%

GLRB variants regulate nearby gene expression in human brain tissues

Yang

Hao

et al. 2017

Sci Rep

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A recent genome-wide association study (GWAS) identified four genetic variants rs78726293, rs191260602, rs17035816 and rs7688285 in GLRB gene to be associated with panic disorder (PD) risk. In fact, GWAS is an important first step to investigate the genetics of human complex diseases. In order to translate into opportunities for new diagnostics and therapies, we must identify the genes perturbed by these four variants, and understand how these variant functionally contributes to the underlying disease pathogenesis. Here, we investigated the effect of these four genetic variants and the expression of three nearby genes including PDGFC, GLRB and GRIA2 in human brain tissues using the GTEx (version 6) and Braineac eQTLs datasets. In GTEx (version 6) dataset, the results showed that both rs17035816 and rs7688285 variants could significantly regulate PDGFC and GLRB gene expression. In Braineac dataset, the results showed that rs17035816 variant could significantly regulate GLRB and GRIA2 gene expression. We believe that these findings further provide important supplementary information about the regulating mechanisms of rs17035816 and rs7688285 variants in PD risk.

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“…However, a large proportion of AD heritability has yet to be explained. However, it is unclear whether cell adhesion molecule (CAM) is present in the Genetic and Environmental Risk for Alzheimer's Disease Consortium (GERAD) GWAS and brain expression GWAS (Bao et al, 2015). Meanwhile, AD GWAS and AD brain expression datasets may provide complementary information to identify important pathways involved in AD (Hochstrasser et al, 2010).…”

Section: Cell Adhesion Moleculementioning

confidence: 99%

The recent development in synthesis and pharmacological evaluation of small molecule to treat Alzheimer's diseases: A review

2020

Int. J. Adv. Biol. Biomed. Res.

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Alzheimer's disease is a neurological disorder in which the death of brain cells causes memory loss and cognitive decline. It is a neurodegenerative type of dementia, the disease starts mild and gets progressively worse. Like all types of dementia, Alzheimer's is caused by brain cell death. The most common presentation marking Alzheimer's dementia is where symptoms of memory loss are the most prominent, especially in the area of learning and recalling new information. Alzheimer's disease is not simple to diagnose for which there is no single test. For this reason, the first thing doctors do is to rule out other problems before confirming whether mental signs and symptoms are severe enough to be a kind of dementia or something else. Genetic test is possible in some settings to indicate the likelihood of someone having or developing the disease but this is controversial and not entirely reliable. There are no disease-modifying drugs available for Alzheimer's disease but some options may reduce its symptoms and help improve quality of life. A different kind of drug, namely memantine, an NMDA receptor antagonist, may also be used, alone or in combination with a cholinesterase inhibitor. This review highlights the several reports that attempt to design and synthesis of some classes of selective Alzheimer's disease inhibitors.

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Cell adhesion molecule pathway genes are regulated by cis-regulatory SNPs and show significantly altered expression in Alzheimer's disease brains

Cited by 39 publications

References 32 publications

Gene expression analysis reveals the dysregulation of immune and metabolic pathways in Alzheimer's disease

Gene expression analysis reveals the dysregulation of immune and metabolic pathways in Alzheimer's disease

GLRB variants regulate nearby gene expression in human brain tissues

The recent development in synthesis and pharmacological evaluation of small molecule to treat Alzheimer's diseases: A review

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