scholarly journals scREAD: A single-cell RNA-Seq database for Alzheimer’s Disease

2020 ◽  
Author(s):  
Jing Jiang ◽  
Cankun Wang ◽  
Ren Qi ◽  
Hongjun Fu ◽  
Qin Ma
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Single Cell ◽  
Rna Sequencing ◽  
Neurodegenerative Disorder ◽  
Supplementary Information ◽  
Cell Type ◽  
Link Type ◽  
Postmortem Brain Tissue ◽  
The Brain

AbstractSummaryAlzheimer’s disease (AD) is a progressive neurodegenerative disorder of the brain and the most common form of dementia among the elderly. The single-cell RNA-sequencing (scRNA-Seq) and single-nucleus RNA-sequencing (snRNA-Seq) techniques are extremely useful for dissecting the function/dysfunction of highly heterogeneous cells in the brain at the single-cell level, and the corresponding data analyses can significantly improve our understanding of why particular cells are vulnerable in AD. We developed an integrated database named scREAD (single-cell RNA-Seq database for Alzheimer’s Disease), which is the first database dedicated to the management of all the existing scRNA-Seq and snRNA-Seq datasets from human postmortem brain tissue with AD and mouse models with AD pathology. scREAD provides comprehensive analysis results for 55 datasets from eight brain regions, including control atlas construction, cell type prediction, identification of differentially expressed genes, and identification of cell-type-specific regulons.Availability and ImplementationscREAD is a one-stop and user-friendly interface and freely available at https://bmbls.bmi.osumc.edu/scread/. The backend workflow can be downloaded from https://github.com/OSU-BMBL/scread/tree/master/script, to enable more discovery-driven [email protected] or [email protected] informationSupplementary data are available at Bioinformatics online.

scholarly journals Sex-stratified single-cell RNA-Seq analysis identifies sex-specific and cell type-specific transcriptional responses in Alzheimer’s disease across two brain regions.

2021 ◽  
Author(s):  
Stella Belonwu ◽  
Yaqiao Li ◽  
Daniel Bunis ◽  
Arjun Rao ◽  
Caroline Warly Solsberg ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Single Cell ◽  
Entorhinal Cortex ◽  
Neurodegenerative Disorder ◽  
Brain Regions ◽  
Specific Gene ◽  
Cell Type ◽  
Transcriptional Responses ◽  
Cell Type Specific

Abstract Alzheimer’s disease (AD) is a pervasive neurodegenerative disorder that disproportionately affects women. Since neural anatomy and disease pathophysiology differ by sex, investigating sex-specific mechanisms in AD pathophysiology can inform new therapeutic approaches for both sexes. Here, we utilized nearly 74,000 cells from human prefrontal and entorhinal cortex samples from the first two publicly available single-cell RNA sequencing AD datasets to study cell type-specific sex-stratified transcriptomic perturbations in AD. Our examination at the single-cell level revealed that sex-specific gene and pathway differences in AD were most prominently observed in glial cells of the prefrontal cortex. In the entorhinal cortex, we observed the same genes and pathways to be perturbed in opposing directions between sexes in AD relative to healthy state. Our findings contribute to growing evidence of sex differences in AD-related transcriptomic changes, which can fuel the development of therapies that may prove more effective at reversing AD pathophysiology.

Electromagnetic field in Alzheimer’s disease: a literature review of recent preclinical and clinical studies

2020 ◽  
Vol 17 ◽  
Author(s):  
Reem Habib Mohamad Ali Ahmad ◽  
Marc Fakhoury ◽  
Nada Lawand
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
In Vivo Studies ◽  
Key Factors ◽  
Potential Benefits ◽  
Preclinical And Clinical Studies ◽  
The Brain

: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the progressive loss of neurons leading to cognitive and memory decay. The main signs of AD include the irregular extracellular accumulation of amyloidbeta (Aβ) protein in the brain and the hyper-phosphorylation of tau protein inside neurons. Changes in Aβ expression or aggregation are considered key factors in the pathophysiology of sporadic and early-onset AD and correlate with the cognitive decline seen in patients with AD. Despite decades of research, current approaches in the treatment of AD are only symptomatic in nature and are not effective in slowing or reversing the course of the disease. Encouragingly, recent evidence revealed that exposure to electromagnetic fields (EMF) can delay the development of AD and improve memory. This review paper discusses findings from in vitro and in vivo studies that investigate the link between EMF and AD at the cellular and behavioural level, and highlights the potential benefits of EMF as an innovative approach for the treatment of AD.

scholarly journals Intermittent Hypoxic Conditioning Rescues Cognition and Mitochondrial Bioenergetic Profile in the Triple Transgenic Mouse Model of Alzheimer’s Disease

2021 ◽  
Vol 22 (1) ◽  
pp. 461
Author(s):  
Sónia C. Correia ◽  
Nuno J. Machado ◽  
Marco G. Alves ◽  
Pedro F. Oliveira ◽  
Paula I. Moreira
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Brain Cortex ◽  
Neurodegenerative Disorder ◽  
Special Focus ◽  
Mitochondrial Bioenergetics ◽  
Related Phenotype ◽  
Brain Resilience ◽  
The Brain

The lack of effective disease-modifying therapeutics to tackle Alzheimer’s disease (AD) is unsettling considering the actual prevalence of this devastating neurodegenerative disorder worldwide. Intermittent hypoxic conditioning (IHC) is a powerful non-pharmacological procedure known to enhance brain resilience. In this context, the aim of the present study was to investigate the potential long-term protective impact of IHC against AD-related phenotype, putting a special focus on cognition and mitochondrial bioenergetics and dynamics. For this purpose, six-month-old male triple transgenic AD mice (3×Tg-AD) were submitted to an IHC protocol for two weeks and the behavioral assessment was performed at 8.5 months of age, while the sacrifice of mice occurred at nine months of age and their brains were removed for the remaining analyses. Interestingly, IHC was able to prevent anxiety-like behavior and memory and learning deficits and significantly reduced brain cortical levels of amyloid-β (Aβ) in 3×Tg-AD mice. Concerning brain energy metabolism, IHC caused a significant increase in brain cortical levels of glucose and a robust improvement of the mitochondrial bioenergetic profile in 3×Tg-AD mice, as mirrored by the significant increase in mitochondrial membrane potential (ΔΨm) and respiratory control ratio (RCR). Notably, the improvement of mitochondrial bioenergetics seems to result from an adaptative coordination of the distinct but intertwined aspects of the mitochondrial quality control axis. Particularly, our results indicate that IHC favors mitochondrial fusion and promotes mitochondrial biogenesis and transport and mitophagy in the brain cortex of 3×Tg-AD mice. Lastly, IHC also induced a marked reduction in synaptosomal-associated protein 25 kDa (SNAP-25) levels and a significant increase in both glutamate and GABA levels in the brain cortex of 3×Tg-AD mice, suggesting a remodeling of the synaptic microenvironment. Overall, these results demonstrate the effectiveness of the IHC paradigm in forestalling the AD-related phenotype in the 3×Tg-AD mouse model, offering new insights to AD therapy and forcing a rethink concerning the potential value of non-pharmacological interventions in clinical practice.

scholarly journals Single-Cell RNA Sequencing in Parkinson’s Disease

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 368
Author(s):  
Shi-Xun Ma ◽  
Su Bin Lim
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Single Cell ◽  
Rna Sequencing ◽  
Rna Degradation ◽  
Postmortem Brain ◽  
Cell Type ◽  
New Findings ◽  
Postmortem Brain Tissue ◽  
Technical Challenges

Single-cell and single-nucleus RNA sequencing (sc/snRNA-seq) technologies have enhanced the understanding of the molecular pathogenesis of neurodegenerative disorders, including Parkinson’s disease (PD). Nonetheless, their application in PD has been limited due mainly to the technical challenges resulting from the scarcity of postmortem brain tissue and low quality associated with RNA degradation. Despite such challenges, recent advances in animals and human in vitro models that recapitulate features of PD along with sequencing assays have fueled studies aiming to obtain an unbiased and global view of cellular composition and phenotype of PD at the single-cell resolution. Here, we reviewed recent sc/snRNA-seq efforts that have successfully characterized diverse cell-type populations and identified cell type-specific disease associations in PD. We also examined how these studies have employed computational and analytical tools to analyze and interpret the rich information derived from sc/snRNA-seq. Finally, we highlighted important limitations and emerging technologies for addressing key technical challenges currently limiting the integration of new findings into clinical practice.

scholarly journals Immunosenescence of Natural Killer Cells, Inflammation, and Alzheimer’s Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Corona Solana ◽  
Raquel Tarazona ◽  
Rafael Solana
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Neurodegenerative Disorder ◽  
The Elderly ◽  
Lymphoid Cells ◽  
Target Cells ◽  
The Brain

Alzheimer’s disease (AD) represents the most common cause of dementia in the elderly. AD is a neurodegenerative disorder characterized by progressive memory loss and cognitive decline. Although the aetiology of AD is not clear, both environmental factors and heritable predisposition may contribute to disease occurrence. In addition, inflammation and immune system alterations have been linked to AD. The prevailing hypothesis as cause of AD is the deposition in the brain of amyloid beta peptides (Aβ). Although Aβ have a role in defending the brain against infections, their accumulation promotes an inflammatory response mediated by microglia and astrocytes. The production of proinflammatory cytokines and other inflammatory mediators such as prostaglandins and complement factors favours the recruitment of peripheral immune cells further promoting neuroinflammation. Age-related inflammation and chronic infection with herpes virus such as cytomegalovirus may also contribute to inflammation in AD patients. Natural killer (NK) cells are innate lymphoid cells involved in host defence against viral infections and tumours. Once activated NK cells secrete cytokines such as IFN-γ and TNF-α and chemokines and exert cytotoxic activity against target cells. In the elderly, changes in NK cell compartment have been described which may contribute to the lower capacity of elderly individuals to respond to pathogens and tumours. Recently, the role of NK cells in the immunopathogenesis of AD is discussed. Although in AD patients the frequency of NK cells is not affected, a high NK cell response to cytokines has been described together with NK cell dysregulation of signalling pathways which is in part involved in this altered behaviour.

Graph Theory-Based Brain Network Connectivity Analysis and Classification of Alzheimer’s Disease

2021 ◽  
Author(s):  
A. Thushara ◽  
C. Ushadevi Amma ◽  
Ansamma John
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Graph Theory ◽  
Neurodegenerative Disorder ◽  
Brain Networks ◽  
Network Connectivity ◽  
Brain Regions ◽  
Brain Network ◽  
Fiber Tracts ◽  
The Brain

Alzheimer’s Disease (AD) is basically a progressive neurodegenerative disorder associated with abnormal brain networks that affect millions of elderly people and degrades their quality of life. The abnormalities in brain networks are due to the disruption of White Matter (WM) fiber tracts that connect the brain regions. Diffusion-Weighted Imaging (DWI) captures the brain’s WM integrity. Here, the correlation betwixt the WM degeneration and also AD is investigated by utilizing graph theory as well as Machine Learning (ML) algorithms. By using the DW image obtained from Alzheimer’s Disease Neuroimaging Initiative (ADNI) database, the brain graph of each subject is constructed. The features extracted from the brain graph form the basis to differentiate between Mild Cognitive Impairment (MCI), Control Normal (CN) and AD subjects. Performance evaluation is done using binary and multiclass classification algorithms and obtained an accuracy that outperforms the current top-notch DWI-based studies.

scholarly journals The interplay between microglial states and major risk factors in Alzheimer’s disease through the eyes of single-cell RNA-sequencing: beyond black and white

2019 ◽  
Vol 122 (4) ◽  
pp. 1291-1296 ◽  
Author(s):  
Djuna von Maydell ◽  
Mehdi Jorfi
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Single Cell ◽  
Rna Sequencing ◽  
Cellular Mechanisms ◽  
Black And White ◽  
Single Cell Rna Sequencing ◽  
Sequencing Studies ◽  
Integral Role

Microglia constitute ~10–20% of glial cells in the adult human brain. They are the resident phagocytic immune cells of the central nervous system and play an integral role as first responders during inflammation. Microglia are commonly classified as “HM” (homeostatic), “M1” (classically activated proinflammatory), or “M2” (alternatively activated). Multiple single-cell RNA-sequencing studies suggest that this discrete classification system does not accurately and fully capture the vast heterogeneity of microglial states in the brain. In fact, a recent single-cell RNA-sequencing study showed that microglia exist along a continuous spectrum of states. This spectrum spans heterogeneous populations of homeostatic and neuropathology-associated microglia in both healthy and Alzheimer’s disease (AD) mouse brains. Major risk factors, such as sex, age, and genes, modulate microglial states, suggesting that shifts along the trajectory might play a causal role in AD pathogenesis. This study provides important insight into the cellular mechanisms of AD and underlines the potential of novel cell-based therapies for AD.

scholarly journals Single cell RNA sequencing of human microglia uncovers a subset that is associated with Alzheimer’s disease

2020 ◽  
Vol 16 (S2) ◽  
Author(s):  
Marta Olah ◽  
Vilas Menon ◽  
Naomi Habib ◽  
Mariko Taga ◽  
Yiyi Ma ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Single Cell ◽  
Rna Sequencing ◽  
Human Microglia ◽  
Single Cell Rna Sequencing

scholarly journals Pleiotropic Protective Effects of Phytochemicals in Alzheimer's Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Sergio Davinelli ◽  
Nadia Sapere ◽  
Davide Zella ◽  
Renata Bracale ◽  
Mariano Intrieri ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Protective Effects ◽  
Drug Candidates ◽  
Molecular Events ◽  
Therapeutic Value ◽  
Phytochemical Compounds ◽  
Multiple Levels ◽  
The Brain

Alzheimer’s disease (AD) is a severe chronic neurodegenerative disorder of the brain characterised by progressive impairment in memory and cognition. In the past years an intense research has aimed at dissecting the molecular events of AD. However, there is not an exhaustive knowledge about AD pathogenesis and a limited number of therapeutic options are available to treat this neurodegenerative disease. Consequently, considering the heterogeneity of AD, therapeutic agents acting on multiple levels of the pathology are needed. Recent findings suggest that phytochemicals compounds with neuroprotective features may be an important resources in the discovery of drug candidates against AD. In this paper we will describe some polyphenols and we will discuss their potential role as neuroprotective agents. Specifically, curcumin, catechins, and resveratrol beyond their antioxidant activity are also involved in antiamyloidogenic and anti-inflammatory mechanisms. We will focus on specific molecular targets of these selected phytochemical compounds highlighting the correlations between their neuroprotective functions and their potential therapeutic value in AD.

scholarly journals Single-cell RNA sequencing reveals B cell–related molecular biomarkers for Alzheimer’s disease

2021 ◽  
Author(s):  
Liu-Lin Xiong ◽  
Lu-Lu Xue ◽  
Ruo-Lan Du ◽  
Rui-Ze Niu ◽  
Li Chen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
B Cells ◽  
B Cell ◽  
Single Cell ◽  
Rna Sequencing ◽  
Early Stage ◽  
Diagnostic Process ◽  
Sequencing Analysis ◽  
Single Cell Rna Sequencing

AbstractIn recent years, biomarkers have been integrated into the diagnostic process and have become increasingly indispensable for obtaining knowledge of the neurodegenerative processes in Alzheimer’s disease (AD). Peripheral blood mononuclear cells (PBMCs) in human blood have been reported to participate in a variety of neurodegenerative activities. Here, a single-cell RNA sequencing analysis of PBMCs from 4 AD patients (2 in the early stage, 2 in the late stage) and 2 normal controls was performed to explore the differential cell subpopulations in PBMCs of AD patients. A significant decrease in B cells was detected in the blood of AD patients. Furthermore, we further examined PBMCs from 43 AD patients and 41 normal subjects by fluorescence activated cell sorting (FACS), and combined with correlation analysis, we found that the reduction in B cells was closely correlated with the patients’ Clinical Dementia Rating (CDR) scores. To confirm the role of B cells in AD progression, functional experiments were performed in early-stage AD mice in which fibrous plaques were beginning to appear; the results demonstrated that B cell depletion in the early stage of AD markedly accelerated and aggravated cognitive dysfunction and augmented the Aβ burden in AD mice. Importantly, the experiments revealed 18 genes that were specifically upregulated and 7 genes that were specifically downregulated in B cells as the disease progressed, and several of these genes exhibited close correlation with AD. These findings identified possible B cell-based AD severity, which are anticipated to be conducive to the clinical identification of AD progression.

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