We have located links that may give you full text access.
PLD3 epigenetic changes in the hippocampus of Alzheimer's disease.
Clinical Epigenetics 2018 September 13
BACKGROUND: Whole-exome sequencing has revealed a rare missense variant in PLD3 gene (rs145999145) to be associated with late onset Alzheimer's disease (AD). Nevertheless, the association remains controversial and little is known about the role of PLD3 in AD. Interestingly, PLD3 encodes a phospholipase that may be involved in amyloid precursor protein (APP) processing. Our aim was to gain insight into the epigenetic mechanisms regulating PLD3 gene expression in the human hippocampus affected by AD.
RESULTS: We assessed PLD3 mRNA expression by qPCR and protein levels by Western blot in frozen hippocampal samples from a cohort of neuropathologically confirmed pure AD cases and controls. Next, we profiled DNA methylation at cytosine-phosphate-guanine dinucleotide (CpG) site resolution by pyrosequencing and further validated results by bisulfite cloning sequencing in two promoter regions of the PLD3 gene. A 1.67-fold decrease in PLD3 mRNA levels (p value < 0.001) was observed in the hippocampus of AD cases compared to controls, and a slight decrease was also found by Western blot at protein level. Moreover, PLD3 mRNA levels inversely correlated with the average area of β-amyloid burden (tau-b = - 0,331; p value < 0.01) in the hippocampus. A differentially methylated region was identified within the alternative promoter of PLD3 gene showing higher DNA methylation levels in the AD hippocampus compared to controls (21.7 ± 4.7% vs. 18.3 ± 4.8%; p value < 0.05).
CONCLUSIONS: PLD3 gene is downregulated in the human hippocampus in AD cases compared to controls. Altered epigenetic mechanisms, such as differential DNA methylation within an alternative promoter of PLD3 gene, may be involved in the pathological processes of AD. Moreover, PLD3 mRNA expression inversely correlates with hippocampal β-amyloid burden, which adds evidence to the hypothesis that PLD3 protein may contribute to AD development by modifying APP processing.
RESULTS: We assessed PLD3 mRNA expression by qPCR and protein levels by Western blot in frozen hippocampal samples from a cohort of neuropathologically confirmed pure AD cases and controls. Next, we profiled DNA methylation at cytosine-phosphate-guanine dinucleotide (CpG) site resolution by pyrosequencing and further validated results by bisulfite cloning sequencing in two promoter regions of the PLD3 gene. A 1.67-fold decrease in PLD3 mRNA levels (p value < 0.001) was observed in the hippocampus of AD cases compared to controls, and a slight decrease was also found by Western blot at protein level. Moreover, PLD3 mRNA levels inversely correlated with the average area of β-amyloid burden (tau-b = - 0,331; p value < 0.01) in the hippocampus. A differentially methylated region was identified within the alternative promoter of PLD3 gene showing higher DNA methylation levels in the AD hippocampus compared to controls (21.7 ± 4.7% vs. 18.3 ± 4.8%; p value < 0.05).
CONCLUSIONS: PLD3 gene is downregulated in the human hippocampus in AD cases compared to controls. Altered epigenetic mechanisms, such as differential DNA methylation within an alternative promoter of PLD3 gene, may be involved in the pathological processes of AD. Moreover, PLD3 mRNA expression inversely correlates with hippocampal β-amyloid burden, which adds evidence to the hypothesis that PLD3 protein may contribute to AD development by modifying APP processing.
Full text links
Related Resources
Trending Papers
Heart failure with preserved ejection fraction: diagnosis, risk assessment, and treatment.Clinical Research in Cardiology : Official Journal of the German Cardiac Society 2024 April 12
Proximal versus distal diuretics in congestive heart failure.Nephrology, Dialysis, Transplantation 2024 Februrary 30
Efficacy and safety of pharmacotherapy in chronic insomnia: A review of clinical guidelines and case reports.Mental Health Clinician 2023 October
World Health Organization and International Consensus Classification of eosinophilic disorders: 2024 update on diagnosis, risk stratification, and management.American Journal of Hematology 2024 March 30
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app