Microglia Mediate the Occurrence and Development of Alzheimer’s Disease Through Ligand-Receptor Axis Communication

Jian, Chongdong; Wei, Lei; Mo, Ruikang; Li, Rongjie; Liang, Lucong; Chen, Liechun; Zou, Chun; Meng, Youshi; Liu, Ying; Zou, Donghua

doi:10.3389/fnagi.2021.731180

Cited by 19 publications

(16 citation statements)

References 48 publications

(51 reference statements)

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“…The higher the level, the more protection against neurodegeneration [ 29 ]. The biological role of IGF1 is mediated through IGF1R, and previous studies have shown that the high IGF1R expression in AD brain tissue is associated with clinicopathology [ 30 ]. Quan et al identified BRWD1 and its corresponding biological processes involved in the development of AD by constructing an AD protein interaction network [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Exploring Early Physical Examination Diagnostic Biomarkers for Alzheimer’s Disease Based on Least Absolute Shrinkage and Selection Operator

Hua

Tang

Liang

et al. 2022

Computational and Mathematical Methods in Medicine

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Neurodegenerative diseases such as Alzheimer’s disease (AD) are an increasing public health challenge. There is an urgent need to shift the focus to accurate detection of clinical AD at the physical examination stage. The purpose of this study was to identify biomarkers for AD diagnosis. Differential expression analysis was performed on a dataset including prefrontal cortical samples and peripheral blood samples of AD to identify shared differentially expressed genes (DEGs) shared between the two datasets. In addition, a minimum absolute contraction and selection operator (LASSO) model based on shared-DEGs identified nine signature genes (MT1X, IGF1, DLEU7, TRIM36, PTPRC, WNK2, SPG20, C8orf59, and BRWD1) that accurately predict AD occurrence. Enrichment analysis showed that the signature gene was significantly associated with the AD-related p53 signaling pathway, T-cell receptor signaling pathway, HIF-1 signaling pathway, AMPK signaling pathway, and FoxO signaling pathway. Thus, our results identify not only biomarkers for diagnosing AD but also potentially specific pathways. The AD biomarkers proposed in this study could serve as indicators for prevention and diagnosis during physical examination.

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Section: Discussionmentioning

confidence: 99%

Exploring Early Physical Examination Diagnostic Biomarkers for Alzheimer’s Disease Based on Least Absolute Shrinkage and Selection Operator

Hua

Tang

Liang

et al. 2022

Computational and Mathematical Methods in Medicine

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“…Limited studies talked about the relationship between MAP4K4 and AD. Jian et al (2021) found MAP4K4 in glial cells could influence the occurrence and development of AD through ligand-receptor axis communication. Considering the protective role of inhibiting MAP4K4 in neurons, future research needs to investigate whether MAP4K4 could mediates the progression of AD in animal studies.…”

Section: Discussionmentioning

confidence: 98%

Identification and Validation of Aging-Related Genes in Alzheimer’s Disease

Zhang

Weng

2022

Front. Neurosci.

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Aging is recognized as the key risk factor for Alzheimer’s disease (AD). This study aimed to identify and verify potential aging-related genes associated with AD using bioinformatics analysis. Aging-related differential expression genes (ARDEGs) were determined by the intersection of limma test, weighted correlation network analysis (WGCNA), and 1153 aging and senescence-associated genes. Potential biological functions and pathways of ARDEGs were determined by GO, KEGG, GSEA, and GSVA. Then, LASSO algorithm was used to identify the hub genes and the diagnostic ability of the five ARDEGs in discriminating AD from the healthy control samples. Further, the correlation between hub ARDEGs and clinical characteristics was explored. Finally, the expression level of the five ARDEGs was validated using other four GEO datasets and blood samples of patients with AD and healthy individuals. Five ARDEGs (GFAP, PDGFRB, PLOD1, MAP4K4, and NFKBIA) were obtained. For biological function analysis, aging, cellular senescence, and Ras protein signal transduction regulation were enriched. Diagnostic ability of the five ARDEGs in discriminating AD from the control samples demonstrated a favorable diagnostic value. Eventually, quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) validation test revealed that compared with healthy controls, the mRNA expression level of PDGFRB, PLOD1, MAP4K4, and NFKBIA were elevated in AD patients. In conclusion, this study identified four ARDEGs (PDGFRB, PLOD1, MAP4K4, and NFKBIA) associated with AD. They provide an insight into potential novel biomarkers for diagnosing AD and monitoring progression.

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“…In this study, REPS1 was identified as a potential biomarker of both disorders and Ras signaling as one of the drivers of pathogenesis. Given that neurodegeneration involves complex networks of interacting genes and pathways ( Jian et al, 2021 ), we adopted a genomic rather than “candidate gene” approach to understanding the landscape of changes that may help explain AD and VD. Our results may aid in the early diagnosis, treatment and even prevention of these debilitating disorders.…”

Section: Discussionmentioning

confidence: 99%

REPS1 as a Potential Biomarker in Alzheimer’s Disease and Vascular Dementia

Luo

Chen²,

Huang³

et al. 2022

Front. Aging Neurosci.

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Vascular dementia (VD) and Alzheimer’s disease (AD) are common types of dementia for which no curative therapies are known. In this study, we identified hub genes associated with AD and VD in order to explore new potential therapeutic targets. Genes differentially expressed in VD and AD in all three datasets (GSE122063, GSE132903, and GSE5281) were identified and used to construct a protein–protein interaction network. We identified 10 modules containing 427 module genes in AD and VD. Module genes showing an area under the diagnostic curve > 0.60 for AD or VD were used to construct a least absolute shrinkage and selection operator model and were entered into a support vector machine-recursive feature elimination algorithm, which identified REPS1 as a hub gene in AD and VD. Furthermore, REPS1 was associated with activation of pyruvate metabolism and inhibition of Ras signaling pathway. Module genes, together with differentially expressed microRNAs from the dataset GSE46579, were used to construct a regulatory network. REPS1 was predicted to bind to the microRNA hsa_miR_5701. Single-sample gene set enrichment analysis was used to explore immune cell infiltration, which suggested a negative correlation between REPS1 expression and infiltration by plasmacytoid dendritic cells in AD and VD. In conclusion, our results suggest core pathways involved in both AD and VD, and they identify REPS1 as a potential biomarker of both diseases. This protein may aid in early diagnosis, monitoring of treatment response, and even efforts to prevent these debilitating disorders.

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Microglia Mediate the Occurrence and Development of Alzheimer’s Disease Through Ligand-Receptor Axis Communication

Cited by 19 publications

References 48 publications

Exploring Early Physical Examination Diagnostic Biomarkers for Alzheimer’s Disease Based on Least Absolute Shrinkage and Selection Operator

Exploring Early Physical Examination Diagnostic Biomarkers for Alzheimer’s Disease Based on Least Absolute Shrinkage and Selection Operator

Identification and Validation of Aging-Related Genes in Alzheimer’s Disease

REPS1 as a Potential Biomarker in Alzheimer’s Disease and Vascular Dementia

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