scholarly journals Impaired Expression of GABA Signaling Components in the Alzheimer’s Disease Middle Temporal Gyrus

2020 ◽  
Vol 21 (22) ◽  
pp. 8704
Author(s):  
Karan Govindpani ◽  
Clinton Turner ◽  
Henry J. Waldvogel ◽  
Richard L. M. Faull ◽  
Andrea Kwakowsky
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gabab Receptor ◽  
Neurodegenerative Disorder ◽  
Middle Temporal Gyrus ◽  
Post Mortem ◽  
Gaba Transporter ◽  
Middle Temporal ◽  
Gaba Signaling ◽  
Signaling Components

γ-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter, playing a central role in the regulation of cortical excitability and the maintenance of the excitatory/inhibitory (E/I) balance. Several lines of evidence point to a remodeling of the cerebral GABAergic system in Alzheimer’s disease (AD), with past studies demonstrating alterations in GABA receptor and transporter expression, GABA synthesizing enzyme activity and focal GABA concentrations in post-mortem tissue. AD is a chronic neurodegenerative disorder with a poorly understood etiology and the temporal cortex is one of the earliest regions in the brain to be affected by AD neurodegeneration. Utilizing NanoString nCounter analysis, we demonstrate here the transcriptional downregulation of several GABA signaling components in the post-mortem human middle temporal gyrus (MTG) in AD, including the GABAA receptor α1, α2, α3, α5, β1, β2, β3, δ, γ2, γ3, and θ subunits and the GABAB receptor 2 (GABABR2) subunit. In addition to this, we note the transcriptional upregulation of the betaine-GABA transporter (BGT1) and GABA transporter 2 (GAT2), and the downregulation of the 67 kDa isoform of glutamate decarboxylase (GAD67), the primary GABA synthesizing enzyme. The functional consequences of these changes require further investigation, but such alterations may underlie disruptions to the E/I balance that are believed to contribute to cognitive decline in AD.

scholarly journals A Machine Learning Approach to Unmask Novel Gene Signatures and Prediction of Alzheimer’s Disease Within Different Brain Regions

2021 ◽  
Author(s):  
Abhibhav Sharma ◽  
Pinki Dey
Keyword(s):  
Machine Learning ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Brain Regions ◽  
Middle Temporal Gyrus ◽  
Non Coding Rna ◽  
Machine Learning Approach ◽  
Microarray Datasets ◽  
Rna Genes

AbstractAlzheimer’s disease (AD) is a progressive neurodegenerative disorder whose aetiology is currently unknown. Although numerous studies have attempted to identify the genetic risk factor(s) of AD, the interpretability and/or the prediction accuracies achieved by these studies remained unsatisfactory, reducing their clinical significance. Here, we employ the ensemble of random-forest and regularized regression model (LASSO) to the AD-associated microarray datasets from four brain regions - Prefrontal cortex, Middle temporal gyrus, Hippocampus, and Entorhinal cortex- to discover novel genetic biomarkers through a machine learning-based feature-selection classification scheme. The proposed scheme unrevealed the most optimum and biologically significant classifiers within each brain region, which achieved by far the highest prediction accuracy of AD in 5-fold cross-validation (99% average). Interestingly, along with the novel and prominent biomarkers including CORO1C, SLC25A46, RAE1, ANKIB1, CRLF3, PDYN, numerous non-coding RNA genes were also observed as discriminator, of which AK057435 and BC037880 are uncharacterized long non-coding RNA genes.

scholarly journals Spatially resolved transcriptomics reveals gene signatures underlying the vulnerability of human middle temporal gyrus in Alzheimer's disease

2021 ◽  
Author(s):  
Shuo Chen ◽  
Yuzhou Chang ◽  
Liangping Li ◽  
Diana Acosta ◽  
Cody Morrison ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Single Molecule ◽  
Brain Region ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Middle Temporal Gyrus ◽  
Middle Temporal ◽  
Spatially Resolved ◽  
Early Alzheimer’S Disease

Abstract Human middle temporal gyrus (MTG) is a vulnerable brain region in early Alzheimer's disease (AD); however, little is known about the molecular mechanisms underlying this regional vulnerability. Here we use the 10x Visium platform to define the spatial topography of gene expression in the MTG from both early AD and control cases. We identify differentially expressed genes (DEGs) and enriched pathways that may contribute to the layer-specific vulnerability of AD pathology. Also, gene co-expression analyses reveal four gene modules, which significantly change their co-expression patterns in the presence of variations of AD pathology. Furthermore, we validate the changes of key representative DEGs that are associated with AD pathology using single-molecule fluorescent in situ hybridization. In summary, we provide a rich resource for the spatial transcriptomic profile of the human MTG, which will contribute to our understanding of the complex architecture and AD pathology of this vulnerable brain region.

A SOFTWARE APPLICATION FOR PREDICTING ALZHEIMER'S DISEASE BASED ON THE LEVEL OF GENE EXPRESSION

2017 ◽  
Author(s):  
Sofiia Yefremova ◽  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gene Expression Data ◽  
Middle Temporal Gyrus ◽  
Expression Data ◽  
Middle Temporal ◽  
Software Application ◽  
The Brain

This article discusses the process of creating a software application that predicts Alzheimer's disease based on gene expression data in healthy and sick patients. The object of the study is the expression samples of genes taken from the study, which used the side of the middle temporal gyrus of the brain of frozen samples.

scholarly journals The middle temporal gyrus is transcriptionally altered in patients with Alzheimer’s Disease.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transcriptional Repression ◽  
Zinc Finger Protein ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Global Gene Expression ◽  
Middle Temporal Gyrus ◽  
Middle Temporal

We sought to understand, at the systems level and in an unbiased fashion, how gene expression was most different in the brains of patients with Alzheimer’s Disease (AD) by mining published microarray datasets (1, 2). Comparing global gene expression profiles between patient and control revealed that a set of 84 genes were expressed at significantly different levels in the middle temporal gyrus (MTG) of patients with Alzheimer’s Disease (1, 2). We used computational analyses to classify these genes into known pathways and existing gene sets, and to describe the major differences in the epigenetic marks at the genomic loci of these genes. While a portion of these genes is computationally cognizable as part of a set of genes up-regulated in the brains of patients with AD (3), many other genes in the gene set identified here have not previously been studied in association with AD. Transcriptional repression, both pre- and post-transcription appears to be affected; nearly 40% of these genes are transcriptional targets of MicroRNA-19A/B (miR-19A/B), the zinc finger protein 10 (ZNF10), or of the AP-1 repressor jun dimerization protein 2 (JDP2).

scholarly journals Reactive astrocytes augment hippocampal inhibitory tone via GABA transporter-3/4 to facilitate synaptic balance in Alzheimer’s disease

2021 ◽  
Author(s):  
Yousif Aldabbagh ◽  
Anam Islam ◽  
Weicong Zhang ◽  
Paul Whiting ◽  
Afia Ali
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tonic Inhibition ◽  
Reactive Astrocytes ◽  
Post Mortem ◽  
Wild Type ◽  
Gaba Transporter ◽  
Synaptic Excitation ◽  
Post Mortem Brain

Background and Purpose: Cognitive decline is a major symptom in Alzheimer’s disease (AD), which is closely associated with synaptic excitatory-inhibitory imbalance. Here, we investigated whether astrocytic mechanisms involving the astrocyte-specific GABA transporter 3/4 (GAT3/4) play a role in altering the synaptic balance in AD and whether these mechanisms correlate with presynaptic cannabinoid type-1 receptors (CB1-Rs). Experimental approach: Using the APPNL-F/NL-F knock-in mouse model of AD, aged-matched to wild-type mice, we performed in vitro electrophysiological whole-cell recordings combined with immunohistochemistry in the CA1 and dentate gyrus (DG) regions of the hippocampus. Comparative neuroanatomy experiments were also performed in post-mortem brain tissue from human AD patients, age-matched to healthy controls. Results: We observed a higher expression of GABA content and GAT3/4 co-localised with reactive astrocytes, which enhanced tonic inhibition in the CA1, and DG of APPNL-F/NL-F mice compared to the age-matched wild-type animals. Blocking GAT3/4 - associated tonic inhibition in APPNL-F/NL-F mice resulted in an enhanced frequency of synaptic excitation, suggesting a presynaptic mechanism. These data also correlated with an up-regulation of CB1-Rs in astrocytes and cholecystokinin (CCK)-containing interneurons, which also enhanced tonic inhibition in the AD model, but did not affect GAT3/4 -associated tonic inhibition. The neuroanatomical results were mirrored in post-mortem tissue of AD patients. Conclusions: Our data suggest that reactive astrocytes lead to augmented tonic inhibition in the hippocampus, which probably plays an important presynaptic compensatory role in attempting to restore AD-associated neuronal hyperactivity. Therefore, reducing tonic inhibition through GAT3/4 may not be a good therapeutic strategy for AD.

Transcriptome Changes in the Alzheimer’s Disease Middle Temporal Gyrus: Importance of RNA Metabolism and Mitochondria-Associated Membrane Genes

2019 ◽  
Vol 70 (3) ◽  
pp. 691-713 ◽  
Author(s):  
Ignazio S. Piras ◽  
Jonida Krate ◽  
Elaine Delvaux ◽  
Jennifer Nolz ◽  
Diego F. Mastroeni ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rna Metabolism ◽  
Middle Temporal Gyrus ◽  
Middle Temporal

Association of AEBP1 and NRN1 RNA expression with Alzheimer’s disease and neurofibrillary tangle density in middle temporal gyrus

2019 ◽  
Vol 1719 ◽  
pp. 217-224
Author(s):  
Ignazio S. Piras ◽  
Jonida Krate ◽  
Elaine Delvaux ◽  
Jennifer Nolz ◽  
Matthew D. De Both ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurofibrillary Tangle ◽  
Middle Temporal Gyrus ◽  
Rna Expression ◽  
Middle Temporal

Auditory Dysfunction in Alzheimer's Disease

2010 ◽  
Vol 15 (1) ◽  
pp. 4-11 ◽  
Author(s):  
Sridhar Krishnamurti
Keyword(s):  
Alzheimer’S Disease ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
Health Care ◽  
Care Setting ◽  
Neurodegenerative Disorder ◽  
Disease Process ◽  
Clinical Protocols ◽  
Speech Language Pathologist ◽  
Auditory Dysfunction

Alzheimer's disease is neurodegenerative disorder which affects a growing number of older adults every year. With an understanding of auditory dysfunction in Alzheimer's disease, the speech-language pathologist working in the health care setting can provide better service to these individuals. The pathophysiology of the disease process in Alzheimer's disease increases the likelihood of specific types of auditory deficits as opposed to others. This article will discuss the auditory deficits in Alzheimer's disease, their implications, and the value of clinical protocols for individuals with this disease.

Acetylcholinesterase Inhibitory Potential and Antioxidant Activities of Five Cultivars of Rosa Damascena Mill. From Isparta, Turkey

2020 ◽  
Vol 18 (4) ◽  
pp. 354-359
Author(s):  
Shirin Tarbiat ◽  
Azize Simay Türütoğlu ◽  
Merve Ekingen
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Free Radical ◽  
Neurodegenerative Disorder ◽  
Antioxidant Activities ◽  
Radical Scavenging ◽  
Acetylcholinesterase Activity ◽  
Rosa Damascena ◽  
Free Radical Damage

Alzheimer's disease is a neurodegenerative disorder characterized by memory loss and impairment of language. Alzheimer's disease is strongly associated with oxidative stress and impairment in the cholinergic pathway, which results in decreased levels of acetylcholine in certain areas of the brain. Hence, inhibition of acetylcholinesterase activity has been recognized as an acceptable treatment against Alzheimer's disease. Nature provides an array of bioactive compounds, which may protect against free radical damage and inhibit acetylcholinesterase activity. This study compares the in vitro antioxidant and anticholinesterase activities of hydroalcoholic extracts of five cultivars of Rosa Damascena Mill. petals (R. damascena 'Bulgarica', R. damascena 'Faik', R. damascena 'Iranica', R. damascena 'Complex-635' and R. damascena 'Complex-637') from Isparta, Turkey. The antioxidant activities of the hydroalcoholic extracts were tested for ferric ion reduction and DPPH radical scavenging activities. The anti-acetylcholinesterase activity was also evaluated. All rose cultivars showed a high potency for scavenging free radical and inhibiting acetylcholinesterase activity. There was a significant correlation between antioxidant and acetylcholinesterase inhibitory activity. Among cultivars, Complex-635 showed the highest inhibitory effect with an IC50 value of 3.92 µg/mL. Our results suggest that all these extracts may have the potential to treat Alzheimer's disease with Complex-635 showing more promise.

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