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Gene expression meta-analysis of Parkinson's disease and its relationship with Alzheimer's disease.

ABSTRACT: Parkinson's disease (PD) and Alzheimer's disease (AD) are the most common neurodegenerative diseases and have been suggested to share common pathological and physiological links. Understanding the cross-talk between them could reveal potentials for the development of new strategies for early diagnosis and therapeutic intervention thus improving the quality of life of those affected. Here we have conducted a novel meta-analysis to identify differentially expressed genes (DEGs) in PD microarray datasets comprising 69 PD and 57 control brain samples which is the biggest cohort for such studies to date. Using identified DEGs, we performed pathway, upstream and protein-protein interaction analysis. We identified 1046 DEGs, of which a majority (739/1046) were downregulated in PD. YWHAZ and other genes coding 14-3-3 proteins are identified as important DEGs in signaling pathways and in protein-protein interaction networks (PPIN). Perturbed pathways also include mitochondrial dysfunction and oxidative stress. There was a significant overlap in DEGs between PD and AD, and over 99% of these were differentially expressed in the same up or down direction across the diseases. REST was identified as an upstream regulator in both diseases. Our study demonstrates that PD and AD share significant common DEGs and pathways, and identifies novel genes, pathways and upstream regulators which may be important targets for therapy in both diseases.

SUBMITTER: Kelly J

PROVIDER: S-EPMC6396547 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Gene expression meta-analysis of Parkinson's disease and its relationship with Alzheimer's disease.

Kelly Jack J Moyeed Rana R Carroll Camille C Albani Diego D Li Xinzhong X

Molecular brain 20190228 1

Parkinson's disease (PD) and Alzheimer's disease (AD) are the most common neurodegenerative diseases and have been suggested to share common pathological and physiological links. Understanding the cross-talk between them could reveal potentials for the development of new strategies for early diagnosis and therapeutic intervention thus improving the quality of life of those affected. Here we have conducted a novel meta-analysis to identify differentially expressed genes (DEGs) in PD microarray da ...[more]

PMID: 30819229

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Project description:ObjectiveTo assess whether dietary fat intake influences Parkinson's disease risk.Data sourcesWe systematically surveyed the Embase and PubMed databases, reviewing manuscripts published prior to October 2018. The following terms were used: ("Paralysis agitans" OR "Parkinson disease" OR "Parkinson" OR "Parkinson's" OR "Parkinson's disease") AND ("fat" OR "dietary fat" OR "dietary fat intake").Data selectionIncluded studies were those with both dietary fat intake and Parkinson's disease risk as exposure factors. The Newcastle-Ottawa Scale was adapted to investigate the quality of included studies. Stata V12.0 software was used for statistical analysis.Outcome measuresThe primary outcomes included the relationship between high total energy intake, high total fat intake, and Parkinson's disease risk. The secondary outcomes included the relationship between different kinds of fatty acids and Parkinson's disease risk.ResultsNine articles met the inclusion criteria and were incorporated into this meta-analysis. Four studies scored 7 and the other five studies scored 9 on the Newcastle-Ottawa Scale, meaning that all studies were of high quality. Meta-analysis results showed that high total energy intake was associated with an increased risk of Parkinson's disease (P = 0.000, odds ratio (OR) = 1.49, 95% confidence interval (CI): 1.26-1.75); in contrast, high total fat intake was not associated with Parkinson's disease risk (P = 0.123, OR = 1.07, 95% CI: 0.91-1.25). Subgroup analysis revealed that polyunsaturated fatty acid intake (P = 0.010, OR = 1.03, 95% CI: 0.88-1.20) reduced the risk of Parkinson's disease, while arachidonic acid (P = 0.026, OR = 1.15, 95% CI: 0.97-1.37) and cholesterol (P = 0.002, OR = 1.09, 95% CI: 0.92-1.29) both increased the risk of Parkinson's disease. Subgroup analysis also demonstrated that, although the results were not significant, consumption of n-3 polyunsaturated fatty acids (P = 0.071, OR = 0.88, 95% CI: 0.73-1.05), ?-linolenic acid (P = 0.06, OR = 0.86, 95% CI: 0.72-1.02), and the n-3 to n-6 ratio (P = 0.458, OR = 0.89, 95% CI: 0.75-1.06) were all linked with a trend toward reduced Parkinson's disease risk. Monounsaturated fatty acid (P = 0.450, OR = 1.06, 95% CI: 0.91-1.23), n-6 polyunsaturated fatty acids (P = 0.100, OR = 1.15, 95% CI: 0.96-1.36) and linoleic acid (P = 0.053, OR = 1.11, 95% CI: 0.94-1.32) intakes were associated with a non-significant trend toward higher PD risk. Saturated fatty acid (P = 0.619, OR = 1.01, 95% CI: 0.87-1.18) intake was not associated with Parkinson's disease.ConclusionDietary fat intake affects Parkinson's disease risk, although this depends on the fatty acid subtype. Higher intake of polyunsaturated fatty acids may reduce the risk of Parkinson's disease, while higher cholesterol and arachidonic acid intakes may elevate Parkinson's disease risk. However, further studies and evidence are needed to validate any link between dietary fat intake and Parkinson's disease.

Dataset Information

Gene expression meta-analysis of Parkinson's disease and its relationship with Alzheimer's disease.

Publications

Gene expression meta-analysis of Parkinson's disease and its relationship with Alzheimer's disease.

Similar Datasets

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