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 Altered Gene Expression Profiles in the Brain, Kidney, and Lung of One-Month-Old Cloned Pigs

2011 ◽  
Vol 13 (3) ◽  
pp. 215-223 ◽  
Author(s):  
Joonghoon Park ◽  
Liangxue Lai ◽  
Melissa Samuel ◽  
David Wax ◽  
Richard S. Bruno ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Altered Gene Expression ◽  
Altered Gene ◽  
The Brain

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 Altered Gene Expression Profiles in the Brain, Kidney, and Lung of Deceased Neonatal Cloned Pigs

2010 ◽  
Vol 12 (5) ◽  
pp. 589-597 ◽  
Author(s):  
Joonghoon Park ◽  
Sadie L. Marjani ◽  
Liangxue Lai ◽  
Melissa Samuel ◽  
David Wax ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Altered Gene Expression ◽  
Altered Gene ◽  
The Brain

scholarly journals Microglia in Alzheimer’s disease

2017 ◽  
Vol 217 (2) ◽  
pp. 459-472 ◽  
Author(s):  
David V. Hansen ◽  
Jesse E. Hanson ◽  
Morgan Sheng
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Genetics ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Inflammatory Factors ◽  
Risk Genes ◽  
Β Amyloid ◽  
The Brain ◽  
Dependent Mechanism

Proliferation and activation of microglia in the brain, concentrated around amyloid plaques, is a prominent feature of Alzheimer’s disease (AD). Human genetics data point to a key role for microglia in the pathogenesis of AD. The majority of risk genes for AD are highly expressed (and many are selectively expressed) by microglia in the brain. There is mounting evidence that microglia protect against the incidence of AD, as impaired microglial activities and altered microglial responses to β-amyloid are associated with increased AD risk. On the other hand, there is also abundant evidence that activated microglia can be harmful to neurons. Microglia can mediate synapse loss by engulfment of synapses, likely via a complement-dependent mechanism; they can also exacerbate tau pathology and secrete inflammatory factors that can injure neurons directly or via activation of neurotoxic astrocytes. Gene expression profiles indicate multiple states of microglial activation in neurodegenerative disease settings, which might explain the disparate roles of microglia in the development and progression of AD pathology.

scholarly journals Microglia-Based Sex-Biased Neuropathology in Early-Stage Alzheimer’s Disease Model Mice and the Potential Pharmacologic Efficacy of Dioscin

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3261
Author(s):  
Xiao Liu ◽  
Qian Zhou ◽  
Jia-He Zhang ◽  
Xiaoying Wang ◽  
Xiumei Gao ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Disease Model ◽  
Amyloid Β ◽  
Brain Lesions ◽  
Synaptic Dysfunction ◽  
Synaptic Loss ◽  
And Function ◽  
The Brain

Alzheimer’s disease (AD), the most common form of dementia, is characterized by amyloid-β (Aβ) accumulation, microglia-associated neuroinflammation, and synaptic loss. The detailed neuropathologic characteristics in early-stage AD, however, are largely unclear. We evaluated the pathologic brain alterations in young adult App knock-in model AppNL-G-F mice at 3 and 6 months of age, which corresponds to early-stage AD. At 3 months of age, microglia expression in the cortex and hippocampus was significantly decreased. By the age of 6 months, the number and function of the microglia increased, accompanied by progressive amyloid-β deposition, synaptic dysfunction, neuroinflammation, and dysregulation of β-catenin and NF-κB signaling pathways. The neuropathologic changes were more severe in female mice than in male mice. Oral administration of dioscin, a natural product, ameliorated the neuropathologic alterations in young AppNL-G-F mice. Our findings revealed microglia-based sex-differential neuropathologic changes in a mouse model of early-stage AD and therapeutic efficacy of dioscin on the brain lesions. Dioscin may represent a potential treatment for AD.

scholarly journals Enhancing microtubule stabilization rescues cognitive deficits and ameliorates pathological phenotype in an amyloidogenic Alzheimer’s disease model

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Juan Jose Fernandez-Valenzuela ◽  
Raquel Sanchez-Varo ◽  
Clara Muñoz-Castro ◽  
Vanessa De Castro ◽  
Elisabeth Sanchez-Mejias ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuroprotective Effect ◽  
Disease Model ◽  
Stabilizing Agents ◽  
Microtubule Stabilization ◽  
Cognitive Improvement ◽  
Epothilone D ◽  
The Impact ◽  
The Brain

Abstract In Alzheimer’s disease (AD), and other tauopathies, microtubule destabilization compromises axonal and synaptic integrity contributing to neurodegeneration. These diseases are characterized by the intracellular accumulation of hyperphosphorylated tau leading to neurofibrillary pathology. AD brains also accumulate amyloid-beta (Aβ) deposits. However, the effect of microtubule stabilizing agents on Aβ pathology has not been assessed so far. Here we have evaluated the impact of the brain-penetrant microtubule-stabilizing agent Epothilone D (EpoD) in an amyloidogenic model of AD. Three-month-old APP/PS1 mice, before the pathology onset, were weekly injected with EpoD for 3 months. Treated mice showed significant decrease in the phospho-tau levels and, more interesting, in the intracellular and extracellular hippocampal Aβ accumulation, including the soluble oligomeric forms. Moreover, a significant cognitive improvement and amelioration of the synaptic and neuritic pathology was found. Remarkably, EpoD exerted a neuroprotective effect on SOM-interneurons, a highly AD-vulnerable GABAergic subpopulation. Therefore, our results suggested that EpoD improved microtubule dynamics and axonal transport in an AD-like context, reducing tau and Aβ levels and promoting neuronal and cognitive protection. These results underline the existence of a crosstalk between cytoskeleton pathology and the two major AD protein lesions. Therefore, microtubule stabilizers could be considered therapeutic agents to slow the progression of both tau and Aβ pathology.

Exploring the brain tissue proteome of TgCRND8 Alzheimer's Disease model mice under B vitamin deficient diet induced hyperhomocysteinemia by LC-MS top-down platform

2019 ◽  
Vol 1124 ◽  
pp. 165-172
Author(s):  
Daniela Delfino ◽  
Diana Valeria Rossetti ◽  
Claudia Martelli ◽  
Ilaria Inserra ◽  
Federica Vincenzoni ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Tissue ◽  
Disease Model ◽  
Top Down ◽  
Deficient Diet ◽  
B Vitamin ◽  
The Brain ◽  
Tissue Proteome

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.

Gene expression profiles of metabolic enzyme transcripts in Alzheimer's disease

2007 ◽  
Vol 1127 ◽  
pp. 127-135 ◽  
Author(s):  
Wendy M. Brooks ◽  
Patrick J. Lynch ◽  
Catherine C. Ingle ◽  
Alexander Hatton ◽  
Piers C. Emson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Metabolic Enzyme
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