Abstract
The occurrence and development of Alzheimer’s disease (AD) is a continuous clinical and pathophysiological process, molecular biological, and brain functional change often appear before clinical symptoms, but the detailed underlying mechanism is still unclear. The expression profiling of postmortem brain tissue from AD patients and controls provides evidence about AD etiopathogenesis. In the current study, we used published AD expression profiling data to construct spatiotemporal specific coexpression networks in AD and analyzed the network preservation features of each brain region in different disease stages to identify the most dramatically changed coexpression modules and obtained AD-related biological pathways, brain regions and circuits, cell types and key genes based on these modules. As result, we constructed 57 spatiotemporal specific networks (19 brain regions by three disease stages) in AD and observed universal expression changes in all 19 brain regions. The eight most dramatically changed coexpression modules were identified in seven brain regions. Genes in these modules are mostly involved in immune response-related pathways and non-neuron cells, and this supports the immune pathology of AD and suggests the role of blood brain barrier (BBB) injuries. Differentially expressed genes (DEGs) meta-analysis and protein–protein interaction (PPI) network analysis suggested potential key genes involved in AD development that might be therapeutic targets. In conclusion, our systematical network analysis on published AD expression profiling data suggests the immunopathogenesis of AD and identifies key brain regions and genes.
Highlights
As the most common form of dementia, Alzheimer’s disease (AD) is a major public health concern
A large number of studies have pointed out that in AD, changes in molecular biological processes and brain function networks often appear before clinical symptoms, brain metabolic homeostasis, such as nerve growth factor metabolic pathway is impaired before clinical AD; a substantial proportion of nondemented older adults have amyloid-beta accumulation and amyloid plaque; lower functional connectivity was observed before cognitive changes by using resting-state MRI (Price et al, 2009; Sperling et al, 2011; Buckley et al, 2017; Pentz et al, 2020), but the detailed underlying mechanism is still unclear
We explored AD-related biological processes by analysing the coexpression gene modules of different brain regions in different disease stages
Summary
As the most common form of dementia, Alzheimer’s disease (AD) is a major public health concern. By using spatial-temporal expression pattern analysis, transcriptome data can provide evidence about specific brain regions and cell types that are possibly related to AD (Wang et al, 2016).
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