scholarly journals Correction: Analyzing Gene Expression from Whole Tissue vs. Different Cell Types Reveals the Central Role of Neurons in Predicting Severity of Alzheimer’s Disease

PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
Author(s):  
Shiri Stempler ◽  
Eytan Ruppin
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Types ◽  
Different Cell Types

scholarly journals Multi-cellular communities are perturbed in the aging human brain and with Alzheimer’s disease

2020 ◽  
Author(s):  
Anael Cain ◽  
Mariko Taga ◽  
Cristin McCabe ◽  
Idan Hekselman ◽  
Charles C. White ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Brain ◽  
Cell Types ◽  
Clinicopathologic Characteristics ◽  
Cellular Environment ◽  
Single Nucleus ◽  
Open Question ◽  
Different Cell Types

AbstractThe role of different cell types and their interactions in Alzheimer’s disease (AD) is an open question that we have pursued by mapping the human brain at the single cell level. Here, we present a high resolution cellular map of the aging frontal cortex by single nucleus RNA-sequencing of 24 individuals with different clinicopathologic characteristics; which we used to infer the cellular architecture of 640 individuals from bulk RNA-seq profiles. Powered by this sample of sufficient size to obtain statistically robust results, we uncovered AD associations with neuronal subtypes and oligodendroglial states. Moreover, we uncovered a network of cellular communities, each composed of different neuronal, glial and endothelial cells subpopulations whose frequencies are correlated across individuals. Two of the cellular communities are altered in relation to cognitive decline and tau pathology. Our work provides a roadmap for evaluating cross-cell type differences in the cellular environment of the AD brain.

scholarly journals TREM2 deficiency eliminates TREM2+ inflammatory macrophages and ameliorates pathology in Alzheimer’s disease mouse models

2015 ◽  
Vol 212 (3) ◽  
pp. 287-295 ◽  
Author(s):  
Taylor R. Jay ◽  
Crystal M. Miller ◽  
Paul J. Cheng ◽  
Leah C. Graham ◽  
Shane Bemiller ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
High Risk ◽  
Mouse Models ◽  
Myeloid Cells ◽  
Cell Types ◽  
Targeted Therapeutics ◽  
Amyloid Deposits ◽  
Inflammatory Macrophages

Variants in triggering receptor expressed on myeloid cells 2 (TREM2) confer high risk for Alzheimer’s disease (AD) and other neurodegenerative diseases. However, the cell types and mechanisms underlying TREM2’s involvement in neurodegeneration remain to be established. Here, we report that TREM2 is up-regulated on myeloid cells surrounding amyloid deposits in AD mouse models and human AD tissue. TREM2 was detected on CD45hiLy6C+ myeloid cells, but not on P2RY12+ parenchymal microglia. In AD mice deficient for TREM2, the CD45hiLy6C+ macrophages are virtually eliminated, resulting in reduced inflammation and ameliorated amyloid and tau pathologies. These data suggest a functionally important role for TREM2+ macrophages in AD pathogenesis and an unexpected, detrimental role of TREM2 in AD pathology. These findings have direct implications for future development of TREM2-targeted therapeutics.

P3-328 Gene expression induced by moderate ischemia indicates a potential role of ischemia-hypoxia regulated genes in Alzheimer's disease

2004 ◽  
Vol 25 ◽  
pp. S448
Author(s):  
Rainald G. Schmidt-Kastner ◽  
Linda Yick ◽  
Cristina Aguirre-Chen ◽  
Isabel Saul ◽  
Christoph Schmitz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Potential Role

Calcium signalling remodelling and disease

2012 ◽  
Vol 40 (2) ◽  
pp. 297-309 ◽  
Author(s):  
Michael J. Berridge
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Bipolar Disorder ◽  
Cardiac Disease ◽  
Calcium Signalling ◽  
Cell Types ◽  
Wide Range ◽  
Inositol 1,4,5 Trisphosphate ◽  
Different Cell Types ◽  
Signalling Systems

A wide range of Ca2+ signalling systems deliver the spatial and temporal Ca2+ signals necessary to control the specific functions of different cell types. Release of Ca2+ by InsP3 (inositol 1,4,5-trisphosphate) plays a central role in many of these signalling systems. Ongoing transcriptional processes maintain the integrity and stability of these cell-specific signalling systems. However, these homoeostatic systems are highly plastic and can undergo a process of phenotypic remodelling, resulting in the Ca2+ signals being set either too high or too low. Such subtle dysregulation of Ca2+ signals have been linked to some of the major diseases in humans such as cardiac disease, schizophrenia, bipolar disorder and Alzheimer's disease.

scholarly journals Type I interferon (IFN)-inducible Absent in Melanoma 2 proteins in neuroinflammation: implications for Alzheimer’s disease

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Divaker Choubey
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Types ◽  
Type I ◽  
Innate Immune Responses ◽  
The Central Nervous System ◽  
Anti Inflammatory ◽  
Species Specific

AbstractCumulative evidence indicates that activation of innate immune responses in the central nervous system (CNS) induces the expression of type 1 interferons (T1 IFNs), a family of cytokines. The T1 IFNs (IFN-α/β), through activation of the JAK/STAT-signaling in microglia, astrocytes, and neurons, induce the expression of IFN-inducible proteins, which mediate the pro- and anti-inflammatory functions of IFNs. Accordingly, T1 IFN-inducible Absent in Melanoma 2 proteins (murine Aim2 and human AIM2) negatively regulate the expression of TI IFNs and, upon sensing higher levels of cytosolic DNA, assemble the Aim2/AIM2 inflammasome, resulting in activation of caspase-1, pyroptosis, and the secretion of pro-inflammatory cytokines (e.g., IL-1β and IL-18). Of interest, studies have indicated a role for the Aim2/AIM2 proteins in neuroinflammation and neurodegenerative diseases, including Alzheimer’s disease (AD). The ability of Aim2/AIM2 proteins to exert pro- and anti-inflammatory effects in CNS may depend upon age, sex hormones, cell-types, and the expression of species-specific negative regulators of the Aim2/AIM2 inflammasome. Therefore, we discuss the role of Aim2/AIM2 proteins in the development of AD. An improved understanding of the role of Absent in Melanoma 2 proteins in AD could identify new approaches to treat patients.

scholarly journals Exosomal miRNAs as Potential Diagnostic Biomarkers in Alzheimer’s Disease

2020 ◽  
Vol 13 (9) ◽  
pp. 243
Author(s):  
Ida Manna ◽  
Selene De Benedittis ◽  
Andrea Quattrone ◽  
Domenico Maisano ◽  
Enrico Iaccino ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Types ◽  
Bioactive Molecules ◽  
Clinical Value ◽  
Rna Sequences ◽  
Exosomal Mirnas ◽  
Preclinical And Clinical Studies ◽  
Internal And External Factors ◽  
Different Cell Types

Alzheimer’s disease (AD), a neurodegenerative disease, is linked to a variety of internal and external factors present from the early stages of the disease. There are several risk factors related to the pathogenesis of AD, among these exosomes and microRNAs (miRNAs) are of particular importance. Exosomes are nanocarriers released from many different cell types, including neuronal cells. Through the transfer of bioactive molecules, they play an important role both in the maintenance of physiological and in pathological conditions. Exosomes could be carriers of potential biomarkers useful for the assessment of disease progression and for therapeutic applications. miRNAs are small noncoding endogenous RNA sequences active in the regulation of protein expression, and alteration of miRNA expression can result in a dysregulation of key genes and pathways that contribute to disease development. Indeed, the involvement of exosomal miRNAs has been highlighted in various neurodegenerative diseases, and this opens the possibility that dysregulated exosomal miRNA profiles may influence AD disease. The advances in exosome-related biomarker detection in AD are summarized. Finally, in this review, we highlight the use of exosomal miRNAs as essential biomarkers in preclinical and clinical studies in Alzheimer’s disease, also taking a look at their potential clinical value.

scholarly journals Differential transcript usage unravels gene expression alterations in Alzheimer’s disease human brains

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Diego Marques-Coelho ◽  
◽  
Lukas da Cruz Carvalho Iohan ◽  
Ana Raquel Melo de Farias ◽  
Amandine Flaig ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Differential Expression ◽  
Cell Types ◽  
Brain Regions ◽  
Adult Brain ◽  
Gene Transcript ◽  
Comprehensive Overview ◽  
Gene Expression Alterations

AbstractAlzheimer’s disease (AD) is the leading cause of dementia in aging individuals. Yet, the pathophysiological processes involved in AD onset and progression are still poorly understood. Among numerous strategies, a comprehensive overview of gene expression alterations in the diseased brain could contribute for a better understanding of the AD pathology. In this work, we probed the differential expression of genes in different brain regions of healthy and AD adult subjects using data from three large transcriptomic studies: Mayo Clinic, Mount Sinai Brain Bank (MSBB), and ROSMAP. Using a combination of differential expression of gene and isoform switch analyses, we provide a detailed landscape of gene expression alterations in the temporal and frontal lobes, harboring brain areas affected at early and late stages of the AD pathology, respectively. Next, we took advantage of an indirect approach to assign the complex gene expression changes revealed in bulk RNAseq to individual cell types/subtypes of the adult brain. This strategy allowed us to identify previously overlooked gene expression changes in the brain of AD patients. Among these alterations, we show isoform switches in the AD causal gene amyloid-beta precursor protein (APP) and the risk gene bridging integrator 1 (BIN1), which could have important functional consequences in neuronal cells. Altogether, our work proposes a novel integrative strategy to analyze RNAseq data in AD and other neurodegenerative diseases based on both gene/transcript expression and regional/cell-type specificities.

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