Gene Expression Biomarkers in the Brain of a Mouse Model for Alzheimer's Disease: Mining of Microarray Data by Logic Classification and Feature Selection

Abstract Alzheimer’s disease is a type of dementia that can cause problems with human memory, thinking and behavior. This disease causes cell death and nerve tissue damage in the brain. The brain damage can be detected using brain volume, whole brain form, and genetic testing. In this research, we propose texture analysis of the brain and genomic analysis to detect Alzheimer’s disease. 3D MRI images were chosen to analyze the texture of the brain, and microarray data were chosen to analyze gene expression. We classified Alzheimer’s disease into three types: Alzheimer’s, Mild Cognitive Impairment (MCI), and Normal. In this study, texture analysis was carried out by using the Advanced Local Binary Pattern (ALBP) and the Gray Level Co-occurrence Matrix (GLCM). We also propose the bi-clustering method to analyze microarray data. The experimental results from texture analysis show that ALBP had better performance than GLCM in classification of Alzheimer’s disease. The ALBP method achieved an average value of accuracy of between 75% - 100% for binary classification of the whole brain data. Furthermore, Biclustering method with microarray data shows good performance gene expression, where this information show influence Alzheimer’s disease with total of bi-cluster is 6.

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Faculty Opinions recommendation of GFAP and vimentin deficiency alters gene expression in astrocytes and microglia in wild-type mice and changes the transcriptional response of reactive glia in mouse model for Alzheimer's disease.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725374290.793547530 ◽

2018 ◽

Author(s):

Michael Klymkowsky

Keyword(s):

Gene Expression ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mouse Model ◽

Transcriptional Response ◽

Wild Type ◽

Reactive Glia

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

International Journal of Molecular Sciences ◽

10.3390/ijms22010461 ◽

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.

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Wide-Ranging Effects on the Brain Proteome in a Transgenic Mouse Model of Alzheimer’s Disease Following Treatment with a Brain-Targeting Somatostatin Peptide

ACS Chemical Neuroscience ◽

10.1021/acschemneuro.1c00303 ◽

2021 ◽

Author(s):

Fadi Rofo ◽

Friederike A. Sandbaumhüter ◽

Aikaterini Chourlia ◽

Nicole G. Metzendorf ◽

Jamie I. Morrison ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mouse Model ◽

Transgenic Mouse ◽

Transgenic Mouse Model ◽

Brain Targeting ◽

Model Of Alzheimer’S Disease ◽

Brain Proteome ◽

The Brain

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Lentivirus-Mediated Expression of Human Secreted Amyloid Precursor Protein-Alpha Promotes Long-Term Induction of Neuroprotective Genes and Pathways in a Mouse Model of Alzheimer’s Disease

Journal of Alzheimer s Disease ◽

10.3233/jad-200757 ◽

2020 ◽

pp. 1-16

Author(s):

Margaret Ryan ◽

Valerie T.Y. Tan ◽

Nasya Thompson ◽

Diane Guévremont ◽

Bruce G. Mockett ◽

...

Keyword(s):

Gene Expression ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mouse Model ◽

Amyloid Precursor Protein ◽

Precursor Protein ◽

Integrated Analysis ◽

Empty Vector ◽

Mouse Transcriptome

Background: Secreted amyloid precursor protein-alpha (sAPPα) can enhance memory and is neurotrophic and neuroprotective across a range of disease-associated insults, including amyloid-β toxicity. In a significant step toward validating sAPPα as a therapeutic for Alzheimer’s disease (AD), we demonstrated that long-term overexpression of human sAPPα (for 8 months) in a mouse model of amyloidosis (APP/PS1) could prevent the behavioral and electrophysiological deficits that develop in these mice. Objective: To explore the underlying molecular mechanisms responsible for the significant physiological and behavioral improvements observed in sAPPα-treated APP/PS1 mice. Methods: We assessed the long-term effects on the hippocampal transcriptome following continuous lentiviral delivery of sAPPα or empty-vector to male APP/PS1 mice and wild-type controls using Affymetrix Mouse Transcriptome Assays. Data analysis was carried out within the Affymetrix Transcriptome Analysis Console and an integrated analysis of the resulting transcriptomic data was performed with Ingenuity Pathway analysis (IPA). Results: Mouse transcriptome assays revealed expected AD-associated gene expression changes in empty-vector APP/PS1 mice, providing validation of the assays used for the analysis. By contrast, there were specific sAPPα-associated gene expression profiles which included increases in key neuroprotective genes such as Decorin, betaine-GABA transporter, and protocadherin beta-5, subsequently validated by qRT-PCR. An integrated biological pathways analysis highlighted regulation of GABA receptor signaling, cell survival, and inflammatory responses. Furthermore, upstream gene regulatory analysis implicated sAPPα activation of Interleukin-4, which can counteract inflammatory changes in AD. Conclusion: This study identified key molecular processes that likely underpin the long-term neuroprotective and therapeutic effects of increasing sAPPα levels in vivo

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Transcriptomic analysis to identify genes associated with selective hippocampal vulnerability in Alzheimer’s disease

Nature Communications ◽

10.1038/s41467-021-22399-3 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Angela M. Crist ◽

Kelly M. Hinkle ◽

Xue Wang ◽

Christina M. Moloney ◽

Billie J. Matchett ◽

...

Keyword(s):

Gene Expression ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Digital Pathology ◽

Selective Vulnerability ◽

Brain Regions ◽

Biochemical Analyses ◽

The Brain ◽

Relevant Gene ◽

Tau Expression

AbstractSelective vulnerability of different brain regions is seen in many neurodegenerative disorders. The hippocampus and cortex are selectively vulnerable in Alzheimer’s disease (AD), however the degree of involvement of the different brain regions differs among patients. We classified corticolimbic patterns of neurofibrillary tangles in postmortem tissue to capture extreme and representative phenotypes. We combined bulk RNA sequencing with digital pathology to examine hippocampal vulnerability in AD. We identified hippocampal gene expression changes associated with hippocampal vulnerability and used machine learning to identify genes that were associated with AD neuropathology, including SERPINA5, RYBP, SLC38A2, FEM1B, and PYDC1. Further histologic and biochemical analyses suggested SERPINA5 expression is associated with tau expression in the brain. Our study highlights the importance of embracing heterogeneity of the human brain in disease to identify disease-relevant gene expression.

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