Polymorphisms of CHAT but not TFAM or VR22 are Associated with Alzheimer Disease Risk

Gao, Lili; Zhang, Yan; Jing-hua, Deng; Yu, Weihong; Yu, Yunxia

doi:10.12659/msm.895984

Cited by 4 publications

(1 citation statement)

References 51 publications

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“…Mutations in one of three genes, amyloid precursor protein ( APP ), presenilins 1 ( PSEN1 ), and presenilins 2 ( PSEN2 ), have been identified to cause alterations in amyloid-beta (Aβ) processing and to lead to AD with complete penetrance [ 5 , 6 ]. The genes might be target markers for therapy of AD [ 7 ], but in complicated AD, a gene does not function alone; instead, multiple genes work together. It is important to correctly uncover and annotate all functional interactions among genes in the cell for any systems-level understanding of cellular functions [ 8 – 10 ]; thus, identification of pathways that are enriched in certain genes perhaps is a good way to reveal the pathological mechanism of hippocampus AD.…”

Section: Introductionmentioning

confidence: 99%

A Novel Method to Identify Differential Pathways in Hippocampus Alzheimer’s Disease

Liu

2017

Med Sci Monit

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BackgroundAlzheimer’s disease (AD) is the most common type of dementia. The objective of this paper is to propose a novel method to identify differential pathways in hippocampus AD.Material/MethodsWe proposed a combined method by merging existed methods. Firstly, pathways were identified by four known methods (DAVID, the neaGUI package, the pathway-based co-expressed method, and the pathway network approach), and differential pathways were evaluated through setting weight thresholds. Subsequently, we combined all pathways by a rank-based algorithm and called the method the combined method. Finally, common differential pathways across two or more of five methods were selected.ResultsPathways obtained from different methods were also different. The combined method obtained 1639 pathways and 596 differential pathways, which included all pathways gained from the four existing methods; hence, the novel method solved the problem of inconsistent results. Besides, a total of 13 common pathways were identified, such as metabolism, immune system, and cell cycle.ConclusionsWe have proposed a novel method by combining four existing methods based on a rank product algorithm, and identified 13 significant differential pathways based on it. These differential pathways might provide insight into treatment and diagnosis of hippocampus AD.

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Section: Introductionmentioning

confidence: 99%

A Novel Method to Identify Differential Pathways in Hippocampus Alzheimer’s Disease

Liu

2017

Med Sci Monit

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Impact of interval training with probiotic (L. plantarum / Bifidobacterium bifidum) on passive avoidance test, ChAT and BDNF in the hippocampus of rats with Alzheimer’s disease

Shamsipour

Sharifi

Taghian

2021

Neuroscience Letters

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CHAT gene polymorphism rs3810950 is associated with the risk of Alzheimer’s disease in the Czech population

et al. 2018

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BackgroundCholinergic hypothesis of Alzheimer’s disease (AD) is based on the findings that a reduced and/or perturbed cholinergic activity in the central nervous system correlates with cognitive decline in patients with Alzheimer’s disease. The hypothesis resulted in the development of centrally-acting agents potentiating cholinergic neurotransmission; these drugs, however, only slowed down the cognitive decline and could not prevent it. Consequently, the perturbation of the central cholinergic signalling has been accepted as a part of the Alzheimer’s aetiology but not necessarily the primary cause of the disease. In the present study we have focused on the rs3810950 polymorphism of ChAT (choline acetyltransferase) gene that has not been studied in Czech population before.MethodsWe carried out an association study to test for a relationship between the rs3810950 polymorphism and Alzheimer’s disease in a group of 1186 persons; 759 patients with Alzheimer’s disease and 427 control subjects. Furthermore, we performed molecular modelling of the terminal domain (1st-126th amino acid residue) of one of the ChAT isoforms (M) to visualise in silico whether the rs3810950 polymorphism (A120T) can change any features of the tertiary structure of the protein which would have a potential to alter its function.ResultsThe AA genotype of CHAT was associated with a 1.25 times higher risk of AD (p < 0.002) thus demonstrating that the rs3810950 polymorphism can have a modest but statistically significant effect on the risk of AD in the Czech population. Furthermore, the molecular modelling indicated that the polymorphism is likely to be associated with significant variations in the tertiary structure of the protein molecule which may impact its enzyme activity.ConclusionsOur findings are consistent with the results of the meta-analytical studies of the relationship between rs3810950 polymorphism and AD and provide further material evidence for a direct (primary) involvement of cholinergic mechanisms in the etiopathogenesis of AD, particularly as a factor in cognitive decline and perturbed conscious awareness commonly observed in patients with AD.

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Polymorphisms of CHAT but not TFAM or VR22 are Associated with Alzheimer Disease Risk

Cited by 4 publications

References 51 publications

A Novel Method to Identify Differential Pathways in Hippocampus Alzheimer’s Disease

A Novel Method to Identify Differential Pathways in Hippocampus Alzheimer’s Disease

Impact of interval training with probiotic (L. plantarum / Bifidobacterium bifidum) on passive avoidance test, ChAT and BDNF in the hippocampus of rats with Alzheimer’s disease

CHAT gene polymorphism rs3810950 is associated with the risk of Alzheimer’s disease in the Czech population

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