Abstract
End-stage Alzheimer's disease (AD) involves drastic modifications in neuronal molecular and cellular processes, but little is known about the dynamics of these modifications during disease initiation and progression. Here, we report meta-analysis of 100 publicly available Microarray datasets using threshold-independent analysis. We found that different patients react to AD progression by variable single transcript alterations which however lead to similar changes in functional gene groups. Stratification by patients' cognitive deterioration pre`sented hippocampal-specific mRNA alterations which involved progressively changed gene categories and indicate changes in epigenetic state and microRNA profiles. In addition, datasets from laser-captured neurofibrillary tangles-free hippocampal neurons and transcript classification by cell types identified many of these changes in neurons. Intriguingly, we discovered that early-onset decline in alternative splicing, protein folding and transport transcripts occur concurrently with decreases in synaptic transmission, whereas at later stages these changes progressed into enhanced oxidative stress and inflammation. Our findings open new venues for identifying novel targets for intervention with AD progression.
Keywords: Alzheimer's disease, disease mechanisms, epigenetics, gene group analysis, microarrays, microRNAs, thresholdindependent statistics, chromatin modifications, laser-captured neurons, transcriptome datasets
Current Alzheimer Research
Title:Threshold-Independent Meta-Analysis of Alzheimer`s Disease Transcriptomes shows Progressive Changes in Hippocampal Functions, Epigenetics and microRNA Regulation
Volume: 9 Issue: 4
Author(s): Shahar Barbash, Hermona Soreq
Affiliation:
Keywords: Alzheimer's disease, disease mechanisms, epigenetics, gene group analysis, microarrays, microRNAs, thresholdindependent statistics, chromatin modifications, laser-captured neurons, transcriptome datasets
Abstract: End-stage Alzheimer's disease (AD) involves drastic modifications in neuronal molecular and cellular processes, but little is known about the dynamics of these modifications during disease initiation and progression. Here, we report meta-analysis of 100 publicly available Microarray datasets using threshold-independent analysis. We found that different patients react to AD progression by variable single transcript alterations which however lead to similar changes in functional gene groups. Stratification by patients' cognitive deterioration pre`sented hippocampal-specific mRNA alterations which involved progressively changed gene categories and indicate changes in epigenetic state and microRNA profiles. In addition, datasets from laser-captured neurofibrillary tangles-free hippocampal neurons and transcript classification by cell types identified many of these changes in neurons. Intriguingly, we discovered that early-onset decline in alternative splicing, protein folding and transport transcripts occur concurrently with decreases in synaptic transmission, whereas at later stages these changes progressed into enhanced oxidative stress and inflammation. Our findings open new venues for identifying novel targets for intervention with AD progression.
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Shahar Barbash, Hermona Soreq , Threshold-Independent Meta-Analysis of Alzheimer`s Disease Transcriptomes shows Progressive Changes in Hippocampal Functions, Epigenetics and microRNA Regulation, Current Alzheimer Research 2012; 9 (4) . https://dx.doi.org/10.2174/156720512800492512
DOI https://dx.doi.org/10.2174/156720512800492512 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
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