Dataset Information

Investigating the energy crisis in Alzheimer disease using transcriptome study.

ABSTRACT: Alzheimer disease (AD) is a devastating neurological disorder, which initiates from hippocampus and proliferates to cortical regions. The neurons of hippocampus require higher energy to preserve the firing pattern. In AD, aberrant energy metabolism is the critical factor for neurodegeneration. However, the reason for the energy crisis in hippocampus neurons is still unresolved. Transcriptome analysis enables us in understanding the underlying mechanism of energy crisis. In this study, we identified variants/differential gene/transcript expression profiles from hippocampus RNA-seq data. We predicted the effect of variants in transcription factor (TF) binding using in silico tools. Further, a hippocampus-specific co-expression and functional interaction network were designed to decipher the relationships between TF and differentially expressed genes (DG). Identified variants predominantly influence TF binding, which subsequently regulates the DG. From the results, we hypothesize that the loss of vascular integrity is the fundamental attribute for the energy crisis, which leads to neurodegeneration.

SUBMITTER: Dharshini SAP

PROVIDER: S-EPMC6898285 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Investigating the energy crisis in Alzheimer disease using transcriptome study.

Dharshini S Akila Parvathy SAP Taguchi Y-H YH Gromiha M Michael MM

Scientific reports 20191206 1

Alzheimer disease (AD) is a devastating neurological disorder, which initiates from hippocampus and proliferates to cortical regions. The neurons of hippocampus require higher energy to preserve the firing pattern. In AD, aberrant energy metabolism is the critical factor for neurodegeneration. However, the reason for the energy crisis in hippocampus neurons is still unresolved. Transcriptome analysis enables us in understanding the underlying mechanism of energy crisis. In this study, we identif ...[more]

PMID: 31811163

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Project description:BackgroundWe previously found temporoparietal-predominant atrophy patterns in the behavioral variant of Alzheimer's disease (bvAD), with relative sparing of frontal regions. Here, we aimed to understand the clinico-anatomical dissociation in bvAD based on alternative neuroimaging markers.MethodsWe retrospectively included 150 participants, including 29 bvAD, 28 "typical" amnestic-predominant AD (tAD), 28 behavioral variant of frontotemporal dementia (bvFTD), and 65 cognitively normal participants. Patients with bvAD were compared with other diagnostic groups on glucose metabolism and metabolic connectivity measured by [18F]FDG-PET, and on subcortical gray matter and white matter hyperintensity (WMH) volumes measured by MRI. A receiver-operating-characteristic-analysis was performed to determine the neuroimaging measures with highest diagnostic accuracy.ResultsbvAD and tAD showed predominant temporoparietal hypometabolism compared to controls, and did not differ in direct contrasts. However, overlaying statistical maps from contrasts between patients and controls revealed broader frontoinsular hypometabolism in bvAD than tAD, partially overlapping with bvFTD. bvAD showed greater anterior default mode network (DMN) involvement than tAD, mimicking bvFTD, and reduced connectivity of the posterior cingulate cortex with prefrontal regions. Analyses of WMH and subcortical volume showed closer resemblance of bvAD to tAD than to bvFTD, and larger amygdalar volumes in bvAD than tAD respectively. The top-3 discriminators for bvAD vs. bvFTD were FDG posterior-DMN-ratios (bvAD<bvFTD), MRI posterior-DMN-ratios (bvAD<bvFTD), MRI salience-network-ratios (bvAD>bvFTD, area under the curve [AUC] range 0.85-0.91, all p < 0.001). The top-3 for bvAD vs. tAD were amygdalar volume (bvAD>tAD), MRI anterior-DMN-ratios (bvAD<tAD), FDG anterior-DMN-ratios (bvAD<tAD, AUC range 0.71-0.84, all p < 0.05).ConclusionsSubtle frontoinsular hypometabolism and anterior DMN involvement may underlie the prominent behavioral phenotype in bvAD.

Dataset Information

Investigating the energy crisis in Alzheimer disease using transcriptome study.

Publications

Investigating the energy crisis in Alzheimer disease using transcriptome study.

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