Patel, H;
Hodges, AK;
Curtis, C;
Lee, SH;
Troakes, C;
Dobson, RJB;
Newhouse, SJ;
(2019)
Transcriptomic analysis of probable asymptomatic and symptomatic alzheimer brains.
Brain, Behavior, and Immunity
, 80
pp. 644-656.
10.1016/j.bbi.2019.05.009.
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Abstract
Individuals with intact cognition and neuropathology consistent with Alzheimer's disease (AD) are referred to as asymptomatic AD (AsymAD). These individuals are highly likely to develop AD, yet transcriptomic changes in the brain which might reveal mechanisms for their AD vulnerability are currently unknown. Entorhinal cortex, frontal cortex, temporal cortex and cerebellum tissue from 27 control, 33 AsymAD and 52 AD human brains were microarray expression profiled. Differential expression analysis identified a significant increase of transcriptomic activity in the frontal cortex of AsymAD subjects, suggesting fundamental changes in AD may initially begin within the frontal cortex region prior to AD diagnosis. Co-expression analysis identified an overactivation of the brain "glutamate-glutamine cycle", and disturbances in the brain energy pathways in both AsymAD and AD subjects, while the connectivity of key hub genes in this network indicates a shift from an already increased cell proliferation in AsymAD subjects to stress response and removal of amyloidogenic proteins in AD subjects. This study provides new insight into the earliest biological changes occurring in the brain prior to the manifestation of clinical AD symptoms and provides new potential therapeutic targets for early disease intervention.
| Type: | Article |
|---|---|
| Title: | Transcriptomic analysis of probable asymptomatic and symptomatic alzheimer brains |
| Location: | Netherlands |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.bbi.2019.05.009 |
| Publisher version: | https://doi.org/10.1016/j.bbi.2019.05.009 |
| Language: | English |
| Additional information: | © 2019 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Alzheimer’s disease, Astrocytes, Brain, Frontal lobe, Gene expression, Gene regulatory networks, Human, Microarray analysis, Mitochondria, Neuropathology |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics > Clinical Epidemiology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10074994 |
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