TionFigure S1 Correlation of log2(fold enrichment) values from MeDIP arrays. a, b, c, Scatterplots of fluorescent intensity ratios from each array. 10,000 probes were randomly chosen to plot out of 720,000 on the array. Each probe is represented with a single dot set at 90 transparency. d, R-values from Pearson correlation test of fluorescence intensity ratios for all probes on each slide. (EPS) Figure S2 Validation of MeDIP array data by bisulfiteor DnmtTKO according to RNAseq analysis. Results include the output from both Cuffdiff and DESeq. (XLS)Table S4 PCR primers used in this study.(XLS)AcknowledgmentsWe thank R. Jaenisch, A. Meissner and T. Magnuson for providing the v6.5, DnmtTKO, and Eed2/2 cell lines.Author ContributionsConceived and designed the experiments: PDS JAH. Performed the experiments: JAH MPM KK. Analyzed the data: JAH. Wrote the paper: PDS JAH.PCR. Validation of peaks of changed DNA methylation in Eed 2 cells by bisulfite PCR. Each line represents an individual clone. Methylated 18325633 CpGs are indicated by filled-in circles. Beneath each2/DNAme and H3K27me3 in Mouse Embryonic Stem Cells
An increasing prevalence for Parkinson’s disease (PD) can be detected in advanced age, with 1 among 60-year-olds and 3 in the 80-year-old age-group [1]. Of note is that patients with PD have a roughly 6-times higher risk to develop a dementia than an age-matched healthy control group [2]. Up to 50 of PD show cognitive decline in terms of a mild cognitive impairment already in early stages that predicts the development of dementia, which can occur in up to 80 of PD patients over the long term [3,4]. The dementia syndrome usually develops after approximately 8 to 10 years and has a strong influence not only on the course of the disease but also on the social environment with higher requirements for families and caretakers during Locytic AECOPD; {P,0.01 vs. the Neutrophilic AECOPD; `P,0.05 vs. the Paucigranulocytic everyday life. The latter causes a psychological strain for the patient and family [5], leading to increased stress during home care [6] with growing need for professional care. The dementia syndrome is also accompaniedwith a worse prognosis as regards disease-progression and life expectancy [7]. Early treatment is critical for the modification of the disease progress as acetylcholine esterase inhibitors have only a delaying effect on worsening of cognitive deficits in early stages when neurodegeneration is not exessively advanced. [8]. Therefore, there is a clear need for a biomarker to define patients at risk. Title Loaded From File Neuropathologically, PDD is characterized by cortical Lewy bodies that also occur in patients with dementia with Lewy bodies. However it is heretofore unclear whether both diseases are a matter of a single one. By definition, diagnosis of PDD is made when the onset of dementia is more than one year after the onset of Parkinsonism whereas DLB should be diagnosed when dementia occurs before or concurrently with Parkinsonism [9,10,11,12,13]. As a rule both PDD and DLB are associated with histological changes of Alzheimer’s disease [14]. It has been shown that Lewy bodies contain alpha-synuclein, a presynaptic filament protein that mainly is expressed in the terminal endings ofSerpin A1 in the Diagnosis of Parkinson-Dementianeurons. Therefore, an obvious working theory is that these Lewy bodies are directly linked to the pathophysiological processes, especially that alpha-synuclein inclusions are mostly present in surviving cells and less so in apoptotic cells, suggesting that these inclusions may play a prot.TionFigure S1 Correlation of log2(fold enrichment) values from MeDIP arrays. a, b, c, Scatterplots of fluorescent intensity ratios from each array. 10,000 probes were randomly chosen to plot out of 720,000 on the array. Each probe is represented with a single dot set at 90 transparency. d, R-values from Pearson correlation test of fluorescence intensity ratios for all probes on each slide. (EPS) Figure S2 Validation of MeDIP array data by bisulfiteor DnmtTKO according to RNAseq analysis. Results include the output from both Cuffdiff and DESeq. (XLS)Table S4 PCR primers used in this study.(XLS)AcknowledgmentsWe thank R. Jaenisch, A. Meissner and T. Magnuson for providing the v6.5, DnmtTKO, and Eed2/2 cell lines.Author ContributionsConceived and designed the experiments: PDS JAH. Performed the experiments: JAH MPM KK. Analyzed the data: JAH. Wrote the paper: PDS JAH.PCR. Validation of peaks of changed DNA methylation in Eed 2 cells by bisulfite PCR. Each line represents an individual clone. Methylated 18325633 CpGs are indicated by filled-in circles. Beneath each2/DNAme and H3K27me3 in Mouse Embryonic Stem Cells
An increasing prevalence for Parkinson’s disease (PD) can be detected in advanced age, with 1 among 60-year-olds and 3 in the 80-year-old age-group [1]. Of note is that patients with PD have a roughly 6-times higher risk to develop a dementia than an age-matched healthy control group [2]. Up to 50 of PD show cognitive decline in terms of a mild cognitive impairment already in early stages that predicts the development of dementia, which can occur in up to 80 of PD patients over the long term [3,4]. The dementia syndrome usually develops after approximately 8 to 10 years and has a strong influence not only on the course of the disease but also on the social environment with higher requirements for families and caretakers during everyday life. The latter causes a psychological strain for the patient and family [5], leading to increased stress during home care [6] with growing need for professional care. The dementia syndrome is also accompaniedwith a worse prognosis as regards disease-progression and life expectancy [7]. Early treatment is critical for the modification of the disease progress as acetylcholine esterase inhibitors have only a delaying effect on worsening of cognitive deficits in early stages when neurodegeneration is not exessively advanced. [8]. Therefore, there is a clear need for a biomarker to define patients at risk. Neuropathologically, PDD is characterized by cortical Lewy bodies that also occur in patients with dementia with Lewy bodies. However it is heretofore unclear whether both diseases are a matter of a single one. By definition, diagnosis of PDD is made when the onset of dementia is more than one year after the onset of Parkinsonism whereas DLB should be diagnosed when dementia occurs before or concurrently with Parkinsonism [9,10,11,12,13]. As a rule both PDD and DLB are associated with histological changes of Alzheimer’s disease [14]. It has been shown that Lewy bodies contain alpha-synuclein, a presynaptic filament protein that mainly is expressed in the terminal endings ofSerpin A1 in the Diagnosis of Parkinson-Dementianeurons. Therefore, an obvious working theory is that these Lewy bodies are directly linked to the pathophysiological processes, especially that alpha-synuclein inclusions are mostly present in surviving cells and less so in apoptotic cells, suggesting that these inclusions may play a prot.
