scholarly journals Cell type‐specific enhancer‐promoter connectivity maps in the human brain and associations with Alzheimer’s disease risk

2020 ◽  
Vol 16 (S3) ◽  
Author(s):  
Alexi Nott ◽  
Inge Holtman ◽  
Nicole Coufal ◽  
Johannes CM Schlachetzki ◽  
Miao Yu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Brain ◽  
Disease Risk ◽  
Cell Type ◽  
Cell Type Specific

scholarly journals Transcribed enhancers in the human brain identify novel disease risk mechanisms

2021 ◽  
Author(s):  
Pengfei Dong ◽  
Gabriel E. Hoffman ◽  
Pasha Apontes ◽  
Jaroslav Bendl ◽  
Samir Rahman ◽  
...  
Keyword(s):  
Human Brain ◽  
Disease Risk ◽  
Association Studies ◽  
Population Level ◽  
Cell Type ◽  
Level Variation ◽  
Functional Interpretation ◽  
Neuropsychiatric Diseases ◽  
Order Of Magnitude ◽  
Cell Type Specific

Enhancer RNAs (eRNAs) constitute an important tissue- and cell-type-specific layer of the regulome. Identification of risk variants for neuropsychiatric diseases within enhancers underscores the importance of understanding the population-level variation of eRNAs in the human brain. We jointly analyzed cell type-specific transcriptome and regulome data to identify 30,795 neuronal and 23,265 non-neuronal eRNAs, expanding the catalog of known human brain eRNAs by an order of magnitude. Examination of the population-level variation of the transcriptome and regulome in 1,382 brain samples identified reproducible changes affecting cis- and trans-co-regulation of eRNA-gene modules in schizophrenia. We show that 13% of schizophrenia heritability is jointly mediated in cis by brain gene and eRNA expression. Inclusion of eRNAs in transcriptome-wide association studies facilitated fine-mapping and functional interpretation of disease loci. Overall, our study characterizes the eRNA-gene regulome and genetic mechanisms in the human cortex in both healthy and disease states.

scholarly journals Cell Type-Specific Human APP Transgene Expression by Hippocampal Interneurons in the Tg2576 Mouse Model of Alzheimer’s Disease

2019 ◽  
Vol 13 ◽  
Author(s):  
Corinna Höfling ◽  
Emira Shehabi ◽  
Peer-Hendrik Kuhn ◽  
Stefan F. Lichtenthaler ◽  
Maike Hartlage-Rübsamen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Transgene Expression ◽  
Tg2576 Mouse ◽  
Cell Type ◽  
Model Of Alzheimer’S Disease ◽  
Cell Type Specific

scholarly journals Single-nucleus transcriptome analysis reveals dysregulation of angiogenic endothelial cells and neuroprotective glia in Alzheimer’s disease

2020 ◽  
Vol 117 (41) ◽  
pp. 25800-25809 ◽  
Author(s):  
Shun-Fat Lau ◽  
Han Cao ◽  
Amy K. Y. Fu ◽  
Nancy Y. Ip
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Endothelial Cells ◽  
Transcriptome Analysis ◽  
Cell Type ◽  
Angiogenic Growth Factors ◽  
Cellular Targets ◽  
Therapeutic Development ◽  
Single Nucleus ◽  
Cell Type Specific

Alzheimer’s disease (AD) is the most common form of dementia but has no effective treatment. A comprehensive investigation of cell type-specific responses and cellular heterogeneity in AD is required to provide precise molecular and cellular targets for therapeutic development. Accordingly, we perform single-nucleus transcriptome analysis of 169,496 nuclei from the prefrontal cortical samples of AD patients and normal control (NC) subjects. Differential analysis shows that the cell type-specific transcriptomic changes in AD are associated with the disruption of biological processes including angiogenesis, immune activation, synaptic signaling, and myelination. Subcluster analysis reveals that compared to NC brains, AD brains contain fewer neuroprotective astrocytes and oligodendrocytes. Importantly, our findings show that a subpopulation of angiogenic endothelial cells is induced in the brain in patients with AD. These angiogenic endothelial cells exhibit increased expression of angiogenic growth factors and their receptors (i.e.,EGFL7,FLT1, andVWF) and antigen-presentation machinery (i.e.,B2MandHLA-E). This suggests that these endothelial cells contribute to angiogenesis and immune response in AD pathogenesis. Thus, our comprehensive molecular profiling of brain samples from patients with AD reveals previously unknown molecular changes as well as cellular targets that potentially underlie the functional dysregulation of endothelial cells, astrocytes, and oligodendrocytes in AD, providing important insights for therapeutic development.

scholarly journals Proteinase-Activated Receptor-2 Exerts Protective and Pathogenic Cell Type-Specific Effects in Alzheimer’s Disease

2007 ◽  
Vol 179 (8) ◽  
pp. 5493-5503 ◽  
Author(s):  
Amir Afkhami-Goli ◽  
Farshid Noorbakhsh ◽  
Avril J. Keller ◽  
Nathalie Vergnolle ◽  
David Westaway ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Type ◽  
Specific Effects ◽  
Cell Type Specific

scholarly journals Cell‐type‐specific and sex‐dependent changes in the chromatin accessibility landscape in late‐onset Alzheimer’s disease brains

2020 ◽  
Vol 16 (S3) ◽  
Author(s):  
Ornit Chiba‐Falek ◽  
Julio Barrera ◽  
Lingyun Song ◽  
Alexias Safi ◽  
Young Jun Yu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Late Onset ◽  
Chromatin Accessibility ◽  
Cell Type ◽  
Cell Type Specific

scholarly journals P4-479: METHODS TO ASSESS CELL-TYPE-SPECIFIC, BIOLOGICAL NETWORKS OF ALZHEIMER'S DISEASE

2019 ◽  
Vol 15 ◽  
pp. P1496-P1496
Author(s):  
Kevin Green ◽  
Elizabeth Blue ◽  
Benjamin A. Logsdon ◽  
Brad Rolf ◽  
Shannon Rose ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Biological Networks ◽  
Cell Type ◽  
Cell Type Specific

scholarly journals Cell Type Specific Expression of Toll-Like Receptors in Human Brains and Implications in Alzheimer’s Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-18 ◽  
Author(s):  
Henriette R. Frederiksen ◽  
Henriette Haukedal ◽  
Kristine Freude
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cellular Response ◽  
The Body ◽  
Cellular Damage ◽  
Whole Body ◽  
Toll Like Receptors ◽  
Cell Type ◽  
Cell Type Specific ◽  
The Brain

Toll-like receptors mediate important cellular immune responses upon activation via various pathogenic stimuli such as bacterial or viral components. The activation and subsequent secretion of cytokines and proinflammatory factors occurs in the whole body including the brain. The subsequent inflammatory response is crucial for the immune system to clear the pathogen(s) from the body via the innate and adaptive immune response. Within the brain, astrocytes, neurons, microglia, and oligodendrocytes all bear unique compositions of Toll-like receptors. Besides pathogens, cellular damage and abnormally folded protein aggregates, such as tau and Amyloid beta peptides, have been shown to activate Toll-like receptors in neurodegenerative diseases such as Alzheimer’s disease. This review provides an overview of the different cell type-specific Toll-like receptors of the human brain, their activation mode, and subsequent cellular response, as well as their activation in Alzheimer’s disease. Finally, we critically evaluate the therapeutic potential of targeting Toll-like receptors for treatment of Alzheimer’s disease as well as discussing the limitation of mouse models in understanding Toll-like receptor function in general and in Alzheimer’s disease.

In vivo imaging of region and cell type specific neocortical neurodegeneration in Alzheimer's disease

2002 ◽  
Vol 109 (5-6) ◽  
pp. 837-855 ◽  
Author(s):  
H. Hampel ◽  
S. J. Teipel ◽  
G. E. Alexander ◽  
O. Pogarell ◽  
S. I. Rapoport ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
In Vivo Imaging ◽  
Cell Type ◽  
Cell Type Specific

P4-230: A GENOMIC AND CELL FUNCTION APPROACH TO IDENTIFYING CELL-TYPE-SPECIFIC BIOLOGICAL NETWORKS IN ALZHEIMER'S DISEASE

2006 ◽  
Vol 14 (7S_Part_29) ◽  
pp. P1530-P1530
Author(s):  
Kevin Green ◽  
Elizabeth Blue ◽  
Benjamin A. Logsdon ◽  
Brad Rolf ◽  
Shannon Rose ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Biological Networks ◽  
Cell Function ◽  
Function Approach ◽  
Cell Type ◽  
Cell Type Specific
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