Abstract
Alzheimer’s disease (AD) is a neurodegenerative disease with unelucidated molecular pathogenesis. Herein, we aimed to identify potential hub genes governing the pathogenesis of AD. The AD datasets of GSE118553 and GSE131617 were collected from the NCBI GEO database. The weighted gene coexpression network analysis (WGCNA), differential gene expression analysis, and functional enrichment analysis were performed to reveal the hub genes and verify their role in AD. Hub genes were validated by machine learning algorithms. We identified modules and their corresponding hub genes from the temporal cortex (TC), frontal cortex (FC), entorhinal cortex (EC), and cerebellum (CE). We obtained 33, 42, 42, and 41 hub genes in modules associated with AD in TC, FC, EC, and CE tissues, respectively. Significant differences were recorded in the expression levels of hub genes between AD and the control group in the TC and EC tissues (P < 0.05). The differences in the expressions of FCGRT, SLC1A3, PTN, PTPRZ1, and PON2 in the FC and CE tissues among the AD and control groups were significant (P < 0.05). The expression levels of PLXNB1, GRAMD3, and GJA1 were statistically significant between the Braak NFT stages of AD. Overall, our study uncovered genes that may be involved in AD pathogenesis and revealed their potential for the development of AD biomarkers and appropriate AD therapeutics targets.
Highlights
Alzheimer’s disease (AD) is a type of dementia, which is commonly associated with β-amyloid and neurofibrillary tangles (NFTs)
Our results found that the expression levels of PLXNB1 and GJA1 based on Braak NFT stages were significant, suggesting that these genes may be involved in AD pathogenesis and have a high potential for the development of AD biomarkers and target drugs. (AsymAD) samples (Table 1)
Consistent with the area under the curve (AUC) of AD classifiers in four tissues, we found that the value of the metrics of AD classifiers was higher in temporal cortex (TC) and entorhinal cortex (EC) tissues than in frontal cortex (FC) and CE tissues
Summary
Alzheimer’s disease (AD) is a type of dementia, which is commonly associated with β-amyloid and neurofibrillary tangles (NFTs). Several studies reported that the distribution of NFTs in the brain is highly associated with cognitive impairment status in AD (Braak and Braak, 1991; Nelson et al, 2012). Braak NFT stages refer to the six stages (I, II, III, IV, V, and VI) of the development of NFTs according to the spatial distribution of tangle-bearing neurons in the brain (Braak et al, 2006a). Whether a large amount of tau protein can be detected in different parts of the AD brain is determined by Braak NFT stages. The pathogenesis of AD remains mostly unclear, several theories have been proposed to explain AD pathogenesis, including tau pathology, oxidative stress, cholinergic neurodegeneration, neuroinflammation, and amyloidosis
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