scholarly journals Expression Profiles of Long Noncoding RNAs in Intranasal LPS-Mediated Alzheimer’s Disease Model in Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Liang Tang ◽  
Lan Liu ◽  
Guangyi Li ◽  
Pengcheng Jiang ◽  
Yan Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Network Analysis ◽  
Expression Profiles ◽  
Disease Model ◽  
Noncoding Rnas ◽  
Memory Loss ◽  
Long Noncoding Rnas ◽  
Specific Effects ◽  
Microarray Expression

Alzheimer’s disease (AD), characterized by memory loss, cognitive decline, and dementia, is a progressive neurodegenerative disease. Although the long noncoding RNAs (lncRNAs) have recently been identified to play a role in the pathogenesis of AD, the specific effects of lncRNAs in AD remain unclear. In present study, we have investigated the expression profiles of lncRNAs in hippocampal of intranasal LPS-mediated Alzheimer’s disease models in mice by microarray method. A total of 395 lncRNAs and 123 mRNAs was detected to express differently in AD models and controls (>2.0 folds,p<0.05). The microarray expression was validated by Quantitative Real-Time-PCR (qRT-PCR). The pathway analysis showed the mRNAs that correlated with lncRNAs were involved in inflammation, apoptosis, and nervous system related pathways. The lncRNA-TFs network analysis suggested the lncRNAs were mostly regulated by HMGA2, ONECUT2, FOXO1, and CDC5L. Additionally, lncRNA-target-TFs network analysis indicated the FOXL1, CDC5L, ONECUT2, and CDX1 to be the TFs most likely to regulate the production of these lncRNAs. This is the first study to investigate lncRNAs expression pattern in intranasal LPS-mediated Alzheimer’s disease model in mice. And these results may facilitate the understanding of the pathogenesis of AD targeting lncRNAs.

scholarly journals The Role of Long Noncoding RNAs in Diabetic Alzheimer’s Disease

2018 ◽  
Vol 7 (11) ◽  
pp. 461 ◽  
Author(s):  
Young-Kook Kim ◽  
Juhyun Song
Keyword(s):  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Glucose Dysregulation ◽  
Near Future ◽  
The Brain

Long noncoding RNAs (lncRNAs) are involved in diverse physiological and pathological processes by modulating gene expression. They have been found to be dysregulated in the brain and cerebrospinal fluid of patients with neurodegenerative diseases, and are considered promising therapeutic targets for treatment. Among the various neurodegenerative diseases, diabetic Alzheimer’s disease (AD) has been recently emerging as an important issue due to several unexpected reports suggesting that metabolic issues in the brain, such as insulin resistance and glucose dysregulation, could be important risk factors for AD. To facilitate understanding of the role of lncRNAs in this field, here we review recent studies on lncRNAs in AD and diabetes, and summarize them with different categories associated with the pathogenesis of the diseases including neurogenesis, synaptic dysfunction, amyloid beta accumulation, neuroinflammation, insulin resistance, and glucose dysregulation. It is essential to understand the role of lncRNAs in the pathogenesis of diabetic AD from various perspectives for therapeutic utilization of lncRNAs in the near future.

scholarly journals Extracellular and intraneuronal HMW-AbetaOs represent a molecular basis of memory loss in Alzheimer's disease model mouse

2011 ◽  
Vol 6 (1) ◽  
pp. 20 ◽  
Author(s):  
Ayumi Takamura ◽  
Yasuhide Okamoto ◽  
Takeshi Kawarabayashi ◽  
Tatsuki Yokoseki ◽  
Masao Shibata ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Basis ◽  
Disease Model ◽  
Memory Loss ◽  
Model Mouse

scholarly journals Integrative in situ mapping of single-cell transcriptional states and tissue histopathology in an Alzheimer's disease model

2022 ◽  
Author(s):  
Hu Zeng ◽  
Jiahao Huang ◽  
Haowen Zhou ◽  
William J. Meilandt ◽  
Borislav Dejanovic ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Single Cell ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Disease Model ◽  
Amyloid Β ◽  
Gene Expression Profiles ◽  
Cellular Mechanisms ◽  
Subcellular Resolution

Amyloid-β plaques and neurofibrillary tau tangles are the neuropathologic hallmarks of Alzheimer's disease (AD), but the spatiotemporal cellular responses and molecular mechanisms underlying AD pathophysiology remain poorly understood. Here we introduce STARmap PLUS to simultaneously map single-cell transcriptional states and disease marker proteins in brain tissues of AD mouse models at subcellular resolution (200 nm). This high-resolution spatial transcriptomics map revealed a core-shell structure where disease-associated microglia (DAM) closely contact amyloid-β plaques, whereas disease-associated astrocytes (DAA) and oligodendrocyte precursor cells (OPC) are enriched in the outer shells surrounding the plaque-DAM complex. Hyperphosphorylated tau emerged mainly in excitatory neurons in the CA1 region accompanied by the infiltration of oligodendrocyte subtypes into the axon bundles of hippocampal alveus. The integrative STARmap PLUS method bridges single-cell gene expression profiles with tissue histopathology at subcellular resolution, providing an unprecedented roadmap to pinpoint the molecular and cellular mechanisms of AD pathology and neurodegeneration.

scholarly journals Effects of <i>Syzygium cumini</i> Seed Extract on the Memory Loss of Alzheimer’s Disease Model Rats

2017 ◽  
Vol 06 (03) ◽  
pp. 53-73
Author(s):  
Shahdat Hossain ◽  
Jahirul Islam ◽  
Sujan Bhowmick ◽  
Mozammel Haque ◽  
Asiqur Rahaman
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Model ◽  
Memory Loss ◽  
Seed Extract ◽  
Syzygium Cumini

scholarly journals Dedifferentiation orchestrated through remodeling of the chromatin landscape defines PSEN1 mutation-induced Alzheimer’s Disease

2019 ◽  
Author(s):  
Andrew B. Caldwell ◽  
Qing Liu ◽  
Gary P. Schroth ◽  
Rudolph E. Tanzi ◽  
Douglas R. Galasko ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Late Onset ◽  
Disease Model ◽  
Memory Loss ◽  
Amyloid Β ◽  
Chromatin Accessibility ◽  
Experimental Models ◽  
Patient Specific

AbstractEarly-Onset Familial Alzheimer’s Disease (EOFAD) is a dominantly inherited neurodegenerative disorder elicited by mutations in the PSEN1, PSEN2, and APP genes1. Hallmark pathological changes and symptoms observed, namely the accumulation of misfolded Amyloid-β (Aβ) in plaques and Tau aggregates in neurofibrillary tangles associated with memory loss and cognitive decline, are understood to be temporally accelerated manifestations of the more common sporadic Late-Onset Alzheimer’s Disease. The complete penetrance of EOFAD-causing mutations has allowed for experimental models which have proven integral to the overall understanding of AD2. However, the failure of pathology-targeting therapeutic development suggests that the formation of plaques and tangles may be symptomatic and not describe the etiology of the disease3,4. Here, we use an integrative, multi-omics approach and systems-level analysis in hiPSC-derived neurons to generate a mechanistic disease model for EOFAD. Using patient-specific cells from donors harboring mutations in PSEN1 differentiated into neurons, we characterize the disease-related gene expression and chromatin accessibility changes by RNA- Seq, ATAC-Seq, and histone methylation ChIP-Seq. We show that the defining disease-causing mechanism of EOFAD is dedifferentiation, primarily through the REST-mediated repression of neuronal lineage specification gene programs and the activation of non-specific germ layer precursor gene programs concomitant with modifications in chromatin accessibility. These gene signature profiles and changes in chromatin topology illustrate that EOFAD neurons traverse the chromatin landscape from an ectodermal origin to a mixed germ lineage state. Further, a reanalysis of existing transcriptomic data from PSEN1 patient brain samples demonstrates that the mechanisms identified in our experimental system recapitulate EOFAD in the human brain. Our results comprise a disease model which describes the mechanisms culminating in dedifferentiation that precede amyloid and tau pathology formation and engender neurodegeneration.

scholarly journals Plaque-associated myeloid cells derive from resident microglia in an Alzheimer’s disease model

2020 ◽  
Vol 217 (4) ◽  
Author(s):  
Erin G. Reed-Geaghan ◽  
Andrew L. Croxford ◽  
Burkhard Becher ◽  
Gary E. Landreth
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Expression Profiles ◽  
Disease Model ◽  
Myeloid Cells ◽  
Gene Expression Profiles ◽  
Altered Gene Expression ◽  
Neuritic Dystrophy ◽  
Altered Gene ◽  
The Brain

Alzheimer’s disease (AD) is accompanied by a robust inflammatory response mediated by plaque-associated myeloid cells of the brain. These cells exhibit altered gene expression profiles and serve as a barrier, preventing neuritic dystrophy. The origin of these cells has been controversial and is of therapeutic importance. Here, we genetically labeled different myeloid populations and unequivocally demonstrated that plaque-associated myeloid cells in the AD brain are derived exclusively from resident microglia, with no contribution from circulating peripheral monocytes.

scholarly journals Distinct Hippocampal Expression Profiles of Long Non-coding RNAs in an Alzheimer’s Disease Model

2016 ◽  
Vol 54 (7) ◽  
pp. 4833-4846 ◽  
Author(s):  
Bo Yang ◽  
Zi-an Xia ◽  
Bingwu Zhong ◽  
Xingui Xiong ◽  
Chenxia Sheng ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Expression Profiles ◽  
Disease Model ◽  
Non Coding Rnas
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