Dementia with Lewy bodies post-mortem brains reveal differentially methylated CpG sites with biomarker potential

  • Weisman, D. & McKeith, I. Dementia with Lewy Bodies. Semin. Neurol. 27, 042–047 (2007).

    Article 

    Google Scholar
     

  • Foguem, C. & Manckoundia, P. Lewy Body Disease: Clinical and Pathological “Overlap Syndrome” Between Synucleinopathies (Parkinson Disease) and Tauopathies (Alzheimer Disease). Curr. Neurol. Neurosci. Rep. 2018 18:5 18, 1–9 (2018).

    CAS 

    Google Scholar
     

  • Jones, S. A. V. & O’Brien, J. T. The prevalence and incidence of dementia with Lewy bodies: a systematic review of population and clinical studies. Psychological Med. 44, 673–683 (2014).

    Article 

    Google Scholar
     

  • McKeith, I. G. et al. Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium. Neurology 89, 88 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Arnaoutoglou, N. A., O’Brien, J. T. & Underwood, B. R. Dementia with Lewy bodies — from scientific knowledge to clinical insights. Nat. Rev. Neurol. 15, 103–112 (2018).

    Article 

    Google Scholar
     

  • Spillantini, M. G., Crowther, R. A., Jakes, R., Hasegawa, M. & Goedert, M. α-Synuclein in filamentous inclusions of Lewy bodies from Parkinson’s disease and dementia with Lewy bodies. Proc. Natl Acad. Sci. 95, 6469–6473 (1998).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sanford, A. M. Lewy Body Dementia. Clin. Geriatr. Med. 34, 603–615 (2018).

    Article 
    PubMed 

    Google Scholar
     

  • Urbizu, A. & Beyer, K. Epigenetics in lewy body diseases: Impact on gene expression, utility as a biomarker, and possibilities for therapy. Int. J Mol. Sci. doi.org/10.3390/ijms21134718 (2020).

  • Singleton, A. B. et al. Clinical and Neuropathological Correlates of Apolipoprotein E Genotype in Dementia with Lewy Bodies. Original Res. Artic. Dement Geriatr. Cogn. Disord. 14, 167–175 (2002).

    Article 
    CAS 

    Google Scholar
     

  • Price, A. et al. Mortality in dementia with Lewy bodies compared with Alzheimer’s dementia: a retrospective naturalistic cohort study. BMJ Open 7, e017504 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jellinger, K. A. Dementia with Lewy Bodies and Parkinson’s Disease-Dementia: Current Perspectives. Int. J. Neurol. Neurotherapy 5, (2018).

  • Capouch, S. D., Farlow, M. R. & Brosch, J. R. A Review of Dementia with Lewy Bodies’ Impact, Diagnostic Criteria and Treatment. Neurol. Ther. 7, 249–263 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Savica, R. et al. Incidence of Dementia With Lewy Bodies and Parkinson Disease Dementia. JAMA Neurol. 70, 1396–1402 (2013).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Huh, T. J., Areán, P. A., Bornfeld, H. & Elite-Marcandonatou, A. The Effectiveness of an Environmental and Behavioral Approach to Treat Behavior Problems in a Patient with Dementia with Lewy Bodies: A Case Study. Ann. long.-term. care: Off. J. Am. Med. Dir. Assoc. 16, 17 (2008).


    Google Scholar
     

  • Agin, A. et al. Environmental exposure to phthalates and dementia with Lewy bodies: contribution of metabolomics. J. Neurol., Neurosurg. Psychiatry 91, 968–974 (2020).

    Article 
    PubMed 

    Google Scholar
     

  • Gitler, A. D. et al. α-Synuclein is part of a diverse and highly conserved interaction network that includes PARK9 and manganese toxicity. Nat. Genet. 41, 308–315 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Uversky, V. N., Li, J., Bower, K. & Fink, A. L. Synergistic effects of pesticides and metals on the fibrillation of α-synuclein: Implications for Parkinson’s disease. NeuroToxicology 23, 527–536 (2002).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Yang, J. et al. CpG demethylation in the neurotoxicity of 1-methyl-4-phenylpyridinium might mediate transcriptional up-regulation of α-synuclein in SH-SY5Y cells. Neurosci. Lett. 659, 124–132 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kwok, J. B. Role of epigenetics in Alzheimer’s and Parkinson’s disease. 2, 671–682 doi.org/10.2217/epi.10.43 (2010).

  • Landgrave-Gómez, J., Mercado-Gómez, O. & Guevara-Guzmán, R. Epigenetic mechanisms in neurological and neurodegenerative diseases. Front. Cell. Neurosci. 9, 58 (2015).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Feng, Y., Jankovic, J. & Wu, Y. C. Epigenetic mechanisms in Parkinson’s disease. J. Neurological Sci. 349, 3–9 (2015).

    Article 
    CAS 

    Google Scholar
     

  • Humphries, C. E. et al. Integrated Whole Transcriptome and DNA Methylation Analysis Identifies Gene Networks Specific to Late-Onset Alzheimer’s Disease. J. Alzheimer’s Dis. 44, 977–987 (2015).

    Article 
    CAS 

    Google Scholar
     

  • Chouliaras, L. et al. Epigenetic regulation in the pathophysiology of Lewy body dementia. Prog. Neurobiol. 192, 101822 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Delgado-Morales, R. & Esteller, M. Opening up the DNA methylome of dementia. Mol. Psychiatry 22, 485–496 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Desplats, P. et al. α-Synuclein Sequesters Dnmt1 from the Nucleus: A NOVEL MECHANISM FOR EPIGENETIC ALTERATIONS IN LEWY BODY DISEASES. J. Biol. Chem. 286, 9031–9037 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Funahashi, Y. et al. DNA methylation changes at SNCA intron 1 in patients with dementia with Lewy bodies. Psychiatry Clin. Neurosci. 71, 28–35 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Tsuchida, T. et al. Methylation changes and aberrant expression of FGFR3 in Lewy body disease neurons. Brain Res. 1697, 59–66 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ozaki, Y. et al. DRD2 methylation to differentiate dementia with Lewy bodies from Parkinson’s disease. Acta Neurologica Scandinavica 141, 177–182 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Sanchez-Mut, J. V. et al. Human DNA methylomes of neurodegenerative diseases show common epigenomic patterns. Transl. Psychiatry 6, e718–e718 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Pihlstrøm, L. et al. Epigenome-wide association study of human frontal cortex identifies differential methylation in Lewy body pathology. medRxiv doi.org/10.1101/2021.10.07.21264552 (2021).

  • Zhang, B. & Horvath, S. A General Framework for Weighted Gene Co-Expression Network Analysis. Stat. Appl. Genet. Mol. Biol. 4, (2005).

  • Langfelder, P. & Horvath, S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinforma. 9, 1–13 (2008).

    Article 

    Google Scholar
     

  • Fortin, J. P., Triche, T. J. & Hansen, K. D. Preprocessing, normalization and integration of the Illumina HumanMethylationEPIC array with minfi. Bioinformatics 33, 558–560 (2017).

    CAS 
    PubMed 

    Google Scholar
     

  • Mansell, G. et al. Guidance for DNA methylation studies: statistical insights from the Illumina EPIC array. 20, (2019).

  • Tulloch, J. et al. APOE DNA methylation is altered in Lewy body dementia. Alzheimer’s Dement.: J. Alzheimer’s Assoc. 14, 889 (2018).

    Article 

    Google Scholar
     

  • Liu, H. C., Hu, C. J., Tang, Y. C. & Chang, J. G. A pilot study for circadian gene disturbance in dementia patients. Neurosci. Lett. 435, 229–233 (2008).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Fernandez, A. F. et al. A DNA methylation fingerprint of 1628 human samples. Genome Research 22, (2012).

  • Peters, T. J. et al. De novo identification of differentially methylated regions in the human genome. Epigenetics Chromatin 8, 1–16 (2015). 2015 8:1.

    Article 

    Google Scholar
     

  • Ernst, J. & Kellis, M. ChromHMM: automating chromatin-state discovery and characterization. Nat. Methods 9, 215–216 (2012). 2012 9:3.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • La Manno, G. et al. Molecular Diversity of Midbrain Development in Mouse, Human, and Stem Cells. Cell 167, 566–580.e19 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Phipson, B., Maksimovic, J. & Oshlack, A. missMethyl: an R package for analyzing data from Illumina’s HumanMethylation450 platform. Bioinformatics 32, 286–288 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Goodman, L. D. et al. Toxic expanded GGGGCC repeat transcription is mediated by the PAF1 complex in C9orf72-associated FTD. Nat. Neurosci. 22, 863–874 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Symmank, J. et al. DNMT1 modulates interneuron morphology by regulating Pak6 expression through crosstalk with histone modifications. 13, 536–556 doi.org/10.1080/15592294.2018.1475980 (2018).

  • Civiero, L. et al. Leucine-rich repeat kinase 2 interacts with p21-activated kinase 6 to control neurite complexity in mammalian brain. J. Neurochemistry 135, 1242–1256 (2015).

    Article 
    CAS 

    Google Scholar
     

  • Civiero, L. et al. PAK6 Phosphorylates 14-3-3γ to Regulate Steady State Phosphorylation of LRRK2. Front. Mol. Neurosci. 0, 417 (2017).

    Article 

    Google Scholar
     

  • Giusto, E., Yacoubian, T. A., Greggio, E. & Civiero, L. Pathways to Parkinson’s disease: a spotlight on 14-3-3 proteins. npj Parkinson’s Dis. 7, 1–14 (2021). 2021 7:1.


    Google Scholar
     

  • Lee, B. D., Dawson, V. L. & Dawson, T. M. Leucine-rich repeat kinase 2 (LRRK2) as a potential therapeutic target in Parkinson’s disease. Trends Pharmacol. Sci. 33, 365–373 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Pair, F. S. & Yacoubian, T. A. 14-3-3 Proteins: Novel Pharmacological Targets in Neurodegenerative Diseases. Trends Pharmacol. Sci. 42, 226–238 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Henderson, A. R. et al. DNA Methylation and Expression Profiles of Whole Blood in Parkinson’s Disease. Front. Genet. 12, 509 (2021).

    Article 

    Google Scholar
     

  • Sherva, R. et al. Identification of Novel Candidate Genes for Alzheimer’s Disease by Autozygosity Mapping using Genome Wide SNP Data. J. Alzheimer’s Dis. 23, 349–359 (2011).

    Article 
    CAS 

    Google Scholar
     

  • Broce, I. et al. Immune-related genetic enrichment in frontotemporal dementia: An analysis of genome-wide association studies. PLOS Med. 15, e1002487 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Watson, C. T. et al. Genome-wide DNA methylation profiling in the superior temporal gyrus reveals epigenetic signatures associated with Alzheimer’s disease. doi.org/10.1186/s13073-015-0258-8 (2016).

  • Young, J. I. et al. Genome-wide brain DNA methylation analysis suggests epigenetic reprogramming in Parkinson disease. 5, (2019).

  • Akila Parvathy Dharshini, S., Taguchi, Y.-H. & Michael Gromiha, M. investigating the energy crisis in Alzheimer disease using transcriptome study. doi.org/10.1038/s41598-019-54782-y

  • Carlson, K. M., Andresen, J. M. & Orr, H. T. Emerging pathogenic pathways in the spinocerebellar ataxias. Curr. Opin. Genet. Dev. 19, 247–253 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Elden, A. C. et al. Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS. Nature 466, 1069–1075 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bai, G. et al. Epigenetic dysregulation of hairy and enhancer of split 4 (HES4) is associated with striatal degeneration in postmortem Huntington brains. Hum. Mol. Genet. 24, 1441–1456 (2015).

    Article 
    PubMed 

    Google Scholar
     

  • Blair, L. J. & Criado-Marrero, M. Contribution of ER stress to tau-mediated toxicity. Alzheimer’s Dement. 17, e052231 (2021).


    Google Scholar
     

  • Garranzo-Asensio, M. et al. Identification of prefrontal cortex protein alterations in Alzheimer’s disease. Oncotarget 9, 10847–10867 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • de Boni, L. et al. Next-Generation Sequencing Reveals Regional Differences of the α-Synuclein Methylation State Independent of Lewy Body Disease. NeuroMolecular Med. 13, 310–320 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Sherwani, S. I. & Khan, H. A. Role of 5-hydroxymethylcytosine in neurodegeneration. Gene 570, 17–24 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kuehner, J. N. et al. 5-hydroxymethylcytosine is dynamically regulated during forebrain organoid development and aberrantly altered in Alzheimer’s disease. Cell Rep. 35, 109042 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Smith, A. R. et al. Parallel profiling of DNA methylation and hydroxymethylation highlights neuropathology-associated epigenetic variation in Alzheimer’s disease. Clin. Epigenetics 11, 1–13 (2019).

    Article 
    CAS 

    Google Scholar
     

  • Booth, M. J. et al. Oxidative bisulfite sequencing of 5-methylcytosine and 5-hydroxymethylcytosine. Nat. Protoc. 8, 1841–1851 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hasin, Y., Seldin, M. & Lusis, A. Multi-omics approaches to disease. Genome Biol. 18, 1–15 (2017).

    Article 

    Google Scholar
     

  • Lemche, E. Early Life Stress and Epigenetics in Late-onset Alzheimer’s Dementia: A Systematic Review. Curr. Genomics 19, 522–602 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Carter, C. J. Convergence of genes implicated in Alzheimer’s disease on the cerebral cholesterol shuttle: APP, cholesterol, lipoproteins, and atherosclerosis. Neurochemistry Int. 50, 12–38 (2007).

    Article 
    CAS 

    Google Scholar
     

  • Graham, S. F. et al. Quantitative Measurement of [Na+] and [K+] in Postmortem Human Brain Tissue Indicates Disturbances in Subjects with Alzheimer’s Disease and Dementia with Lewy Bodies. J. Alzheimer’s Dis. 44, 851–857 (2015).

    Article 
    CAS 

    Google Scholar
     

  • Akyol, S. et al. Evidence that the Kennedy and polyamine pathways are dysregulated in human brain in cases of dementia with Lewy bodies. Brain Res. 1743, 146897 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Francis, P. T., Costello, H. & Hayes, G. M. Brains for Dementia Research: Evolution in a Longitudinal Brain Donation Cohort to Maximize Current and Future Value. J. Alzheimer’s Dis. 66, 1635–1644 (2018).

    Article 

    Google Scholar
     

  • Francis, P. T., Hayes, G. M., Costello, H. & Whitfield, D. R. Brains for Dementia Research: The Importance of Cohorts in Brain Banking. Neurosci. Bull. 35, 289 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Aryee, M. J. et al. Minfi: a flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays. Bioinformatics 30, 1363–1369 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Triche, T. J., Weisenberger, D. J., Van Den Berg, D., Laird, P. W. & Siegmund, K. D. Low-level processing of Illumina Infinium DNA Methylation BeadArrays. Nucleic Acids Res. 41, e90–e90 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Pidsley, R. et al. Critical evaluation of the Illumina MethylationEPIC BeadChip microarray for whole-genome DNA methylation profiling. Genome Biol. 17, (2016).

  • Fortin, J. P. et al. Functional normalization of 450k methylation array data improves replication in large cancer studies. Genome Biol. 15, 503 (2014).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Du, P. et al. Comparison of Beta-value and M-value methods for quantifying methylation levels by microarray analysis. BMC Bioinforma. 11, 1–9 (2010).

    Article 

    Google Scholar
     

  • Smyth, G. K. limma: Linear Models for Microarray Data. Bioinformatics and Computational Biology Solutions Using R and Bioconductor 397–420 doi.org/10.1007/0-387-29362-0_23 (2005).

  • Graw, S., Henn, R., Thompson, J. A. & Koestler, D. C. PwrEWAS: A user-friendly tool for comprehensive power estimation for epigenome wide association studies (EWAS). BMC Bioinforma. 20, 1–11 (2019).

    Article 

    Google Scholar
     

  • Zhou, Y. et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat. Commun. 10, 1–10 (2019).


    Google Scholar
     

  • Read more here: Source link