Peripheral Blood MicroRNA Expression Profiles in Alzheimer’s Disease: Screening, Validation, Association with Clinical Phenotype and Implications for Molecular Mechanism

Background Alzheimer’s disease (AD) is an age-related neurodegenerative disease caused by central nervous system disorders. Late-onset Alzheimer disease (LOAD) is the most common neurodegenerative disorder worldwide. Differences at the expression level of certain genes, resulting from either genetic variations or environmental interactions, might be one of the mechanisms underlying differential risks for developing AD. Peripheral blood genome transcriptional profiling may provide a powerful and minimally invasive tool for the identification of novel targets beyond Aβ and tau for AD research. Methods This preliminary study explores molecular pathogenesis of LOAD-related inflammation through next generation sequencing, to assess RNA expression profiles in peripheral blood from five patients with LOAD and 10 healthy controls. Results The analysis of RNA expression profiles revealed 94 genes up-regulated and 147 down-regulated. Gene function analysis, including Gene Ontology (GO) and KOBAS-Kyoto Encyclopedia of DEGs and Genomes (KEGG) pathways indicated upregulation of interferon family (INF) signaling, while the down-regulated genes were mainly associated with the cell cycle process. KEGG metabolic pathways mapping showed gene expression alterations in the signaling pathways of JAK/STAT, chemokines, MAP kinases and Alzheimer disease. The results of this preliminary study provided not only a comprehensive picture of gene expression, but also the key processes associated with pathology for the regulation of neuroinflammation, to improve the current mechanisms to treat LOAD.

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Association between methylation of BIN1 promoter in peripheral blood and preclinical Alzheimer’s disease

Translational Psychiatry ◽

10.1038/s41398-021-01218-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hao Hu ◽

Lan Tan ◽

Yan-Lin Bi ◽

Wei Xu ◽

Lin Tan ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Peripheral Blood ◽

Late Onset ◽

Early Stage ◽

Susceptibility Gene ◽

Subjective Cognitive Decline ◽

Preclinical Ad ◽

T Tau ◽

New Evidence

AbstractThe bridging integrator 1 (BIN1) gene is the second most important susceptibility gene for late-onset Alzheimer’s disease (LOAD) after apolipoprotein E (APOE) gene. To explore whether the BIN1 methylation in peripheral blood changed in the early stage of LOAD, we included 814 participants (484 cognitively normal participants [CN] and 330 participants with subjective cognitive decline [SCD]) from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) database. Then we tested associations of methylation of BIN1 promoter in peripheral blood with the susceptibility for preclinical AD or early changes of cerebrospinal fluid (CSF) AD-related biomarkers. Results showed that SCD participants with significant AD biological characteristics had lower methylation levels of BIN1 promoter, even after correcting for covariates. Hypomethylation of BIN1 promoter were associated with decreased CSF Aβ42 (p = 0.0008), as well as increased p-tau/Aβ42 (p = 0.0001) and t-tau/Aβ42 (p < 0.0001) in total participants. Subgroup analysis showed that the above associations only remained in the SCD subgroup. In addition, hypomethylation of BIN1 promoter was also accompanied by increased CSF p-tau (p = 0.0028) and t-tau (p = 0.0130) in the SCD subgroup, which was independent of CSF Aβ42. Finally, above associations were still significant after correcting single nucleotide polymorphic sites (SNPs) and interaction of APOE ɛ4 status. Our study is the first to find a robust association between hypomethylation of BIN1 promoter in peripheral blood and preclinical AD. This provides new evidence for the involvement of BIN1 in AD, and may contribute to the discovery of new therapeutic targets for AD.

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Molecular Mechanism of Amyloidogenicity and Neurotoxicity of a Pro-aggregated Tau Mutant in the Presence of Histidine Tautomerism via Replica-Exchange Simulation.

Physical Chemistry Chemical Physics ◽

10.1039/d1cp00105a ◽

2021 ◽

Author(s):

Sompriya Chatterjee ◽

Abbas Salimi ◽

Jin Yong Lee

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Molecular Mechanism ◽

Replica Exchange

The accumulation of ΔK280 tau mutant resulting in neurotoxic oligomeric aggregates is an important but yet mysterious procedure in Alzheimer’s disease (AD) development. Recently, we proposed a histidine tautomerization hypothesis...

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Differential Expression of mRNAs in Peripheral Blood Related to Prodrome and Progression of Alzheimer’s Disease

BioMed Research International ◽

10.1155/2020/4505720 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Weishuang Xue ◽

Jinwei Li ◽

Kailei Fu ◽

Weiyu Teng

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Peripheral Blood ◽

Bioinformatics Analysis ◽

Gene Expression Omnibus ◽

Venn Diagram ◽

Ppi Network ◽

Hub Genes ◽

Protein Protein Interaction ◽

Ppi Networks

Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disease that affects the quality of life of elderly individuals, while the pathogenesis of AD is still unclear. Based on the bioinformatics analysis of differentially expressed genes (DEGs) in peripheral blood samples, we investigated genes related to mild cognitive impairment (MCI), AD, and late-stage AD that might be used for predicting the conversions. Methods. We obtained the DEGs in MCI, AD, and advanced AD patients from the Gene Expression Omnibus (GEO) database. A Venn diagram was used to identify the intersecting genes. Gene Ontology (GO) and Kyoto Gene and Genomic Encyclopedia (KEGG) were used to analyze the functions and pathways of the intersecting genes. Protein-protein interaction (PPI) networks were constructed to visualize the network of the proteins coded by the related genes. Hub genes were selected based on the PPI network. Results. Bioinformatics analysis indicated that there were 61 DEGs in both the MCI and AD groups and 27 the same DEGs among the three groups. Using GO and KEGG analyses, we found that these genes were related to the function of mitochondria and ribosome. Hub genes were determined by bioinformatics software based on the PPI network. Conclusions. Mitochondrial and ribosomal dysfunction in peripheral blood may be early signs in AD patients and related to the disease progression. The identified hub genes may provide the possibility for predicting AD progression or be the possible targets for treatments.

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P4-129: Alzheimer's disease: Molecular mechanism of anesthetics induced ABETA peptide oligomerization using spectroscopy

Alzheimer s & Dementia ◽

10.1016/j.jalz.2006.05.1868 ◽

2006 ◽

Vol 2 ◽

pp. S553-S554

Author(s):

Pravat K. Mandal ◽

Jay W. Pettegrew ◽

K. Panchalingam ◽

Ratna Mandal

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Molecular Mechanism ◽

Abeta Peptide

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Innate phagocytosis by peripheral blood monocytes is altered in Alzheimer’s disease

Acta Neuropathologica ◽

10.1007/s00401-016-1596-3 ◽

2016 ◽

Vol 132 (3) ◽

pp. 377-389 ◽

Cited By ~ 17

Author(s):

Ben J. Gu ◽

◽

Xin Huang ◽

Amber Ou ◽

Alan Rembach ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Peripheral Blood ◽

Blood Monocytes ◽

Peripheral Blood Monocytes

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P4-006: Molecular mechanism for induction of neuronal death by beta amyloid protein in Alzheimer's disease

Alzheimer s & Dementia ◽

10.1016/j.jalz.2006.05.1744 ◽

2006 ◽

Vol 2 ◽

pp. S515-S515

Author(s):

Farhan Ul Haq Subhani

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Molecular Mechanism ◽

Neuronal Death ◽

Beta Amyloid ◽

Amyloid Protein ◽

Beta Amyloid Protein

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Comprehensive Analysis of Differential Expression Profiles of Long Non-coding RNAs with Associated Co-expression and Competing Endogenous RNA Networks in the Hippocampus of Patients with Alzheimer's Disease

Current Alzheimer Research ◽

10.2174/1567205018666211202143449 ◽

2021 ◽

Vol 18 ◽

Author(s):

Jian-Jun Zhang ◽

Ze-Xuan-Zhu ◽

Guang-Min-Xu ◽

Peng Su ◽

Qian Lei ◽

...

Keyword(s):

Gene Expression ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Expression Profiles ◽

Gene Expression Omnibus ◽

Competing Endogenous Rna ◽

Pathogenic Genes ◽

Non Coding Rna ◽

Using Data ◽

Trans Regulation

Background: Alzheimer's disease (AD) is still one of the major threats to human health. Although a satisfactory treatment for AD has not yet been discovered, it is necessary to continue to search for novel approaches to deal with this insidious and debilitating disease. Although numerous studies have shown that long non-coding RNA (lncRNA) occupy a significant role in a variety of diseases, their roles in AD remain unclear. Objectives: Using data analysis to explore the role of lncRNA in the course of AD, to further our understanding of AD, and to look forward to finding a new breakthrough for the treatment of AD. Methods: We downloaded and screened expression data of the hippocampal regions of patients with AD from the Gene Expression Omnibus database. We generated lncRNA-miRNA-mRNA networks based on the competing endogenous RNA (ceRNA) hypothesis, and according to gene expression level, we constructed a coding-noncoding co-expression (CNC) network and then executed cis- and trans-regulation analyses. Results: Through comprehensive and systematic analyses, we found that lncRNAs MALAT1, OIP5-AS1, LINC00657, and lnc-NUMB-1 regulated the expression of the key AD pathogenic genes APP, PSEN1, BACE1; and that these lncRNAs may promote the distribution of β-amyloid (Aβ protein) in the brain through exosomes. In addition, lncRNAs were found to adjust viral transcriptional expression, thereby further supporting viral pathogenesis for AD. Conclusions: The lncRNAs MALAT1, OIP5-AS1, LINC00657, and lnc-NUMB-1 that are present in the hippocampus of AD patients exert an important influence on the development of this disease.

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