21 results on '"Chang En Yu"'
Search Results
2. APOE DNA methylation is altered in Lewy body dementia
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Eliezer Masliah, Peter T. Nelson, Julia Kofler, Randy Woltjer, Jeffrey Kaye, Lesley Leong, Douglas Galasko, James B. Leverenz, Chang En Yu, Oscar L. Lopez, Sunny Chen, Gregory A. Jicha, Jessica Tulloch, C. Dirk Keene, Janna H. Neltner, Andrew Shutes-David, Steven P. Millard, and Debby W. Tsuang
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Lewy Body Disease ,Male ,0301 basic medicine ,Apolipoprotein E ,medicine.medical_specialty ,Genotype ,Epidemiology ,Biology ,Article ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Apolipoproteins E ,0302 clinical medicine ,Developmental Neuroscience ,Alzheimer Disease ,Internal medicine ,medicine ,Humans ,Dementia ,Epigenetics ,Allele ,Alleles ,Aged ,Aged, 80 and over ,Lewy body ,Health Policy ,Brain ,Methylation ,DNA Methylation ,medicine.disease ,Frontal Lobe ,Psychiatry and Mental health ,030104 developmental biology ,Endocrinology ,Frontal lobe ,DNA methylation ,Female ,lipids (amino acids, peptides, and proteins) ,Autopsy ,Neurology (clinical) ,Geriatrics and Gerontology ,hormones, hormone substitutes, and hormone antagonists ,030217 neurology & neurosurgery - Abstract
Introduction Inheritance of the e4 allele of apolipoprotein E ( APOE ) increases a person's risk of developing both Alzheimer's disease (AD) and Lewy body dementia (LBD), yet the underlying mechanisms behind this risk are incompletely understood. The recent identification of reduced APOE DNA methylation in AD postmortem brains prompted this study to investigate APOE methylation in LBD. Methods Genomic DNA from postmortem brain tissues (frontal lobe and cerebellum) of neuropathological pure (np) controls and npAD, LBD + AD, and npLBD subjects were bisulfite pyrosequenced. DNA methylation levels of two APOE subregions were then compared for these groups. Results APOE DNA methylation was significantly reduced in npLBD compared with np controls, and methylation levels were lowest in the LBD + AD group. Discussion Given that npLBD and npAD postmortem brains shared a similar reduction in APOE methylation, it is possible that an aberrant epigenetic change in APOE is linked to risk for both diseases.
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- 2018
3. P4-089: APOE RNA PRODUCTION IS MODULATED BY DNA METHYLATION NEAR ε2/ε3/ε4 DEFINING SNPS
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Jessica Tulloch, Steve Millard, Lesley Leong, Sunny Chen, Kaitlin Todd, Eun-Gyung Lee, and Chang En Yu
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Apolipoprotein E ,Genetics ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,DNA methylation ,RNA ,Single-nucleotide polymorphism ,Neurology (clinical) ,Geriatrics and Gerontology ,Biology - Published
- 2019
4. Inheritance Model Introduces Differential Bias in CNV Calls Between Parents and Offspring
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Dorcas J. Dobie, Sulgi Kim, Ellen M. Wijsman, Lesley Leong, Allen D. Radant, Steven P. Millard, Chang En Yu, and Debby W. Tsuang
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Genetics ,Epidemiology ,Inheritance (genetic algorithm) ,Inference ,Single-nucleotide polymorphism ,Pedigree chart ,Genome-wide association study ,Computational biology ,Biology ,eye diseases ,symbols.namesake ,Mendelian inheritance ,symbols ,Copy-number variation ,Genetics (clinical) ,Genetic association - Abstract
Copy Number Variation (CNV) is increasingly implicated in disease pathogenesis. CNVs are often identified by statistical models applied to data from single nucleotide polymorphism (SNP) panels. Family information for samples provides additional information for CNV inference. Two modes of PennCNV (the Joint-call and Posterior-call), which are some of the most well-developed family-based CNV calling methods, use a “Joint-model” as a main component. This models all family members’ CNV states together with Mendelian inheritance. Methods based on the Joint-model are used to infer CNV calls of cases and controls in a pedigree, which may be compared to each other to test an association. Although benefits from the Joint-model have been shown elsewhere, equality of call rates in parents and offspring has not been evaluated previously. This can affect downstream analyses in studies that compare CNV rates in cases versus controls in pedigrees. In this paper, we show that the Joint-model can introduce different CNV call rates among family members in the absence of a true difference. First, we show that the Joint-model may analytically introduce differential CNV calls because of asymmetry of the model. We demonstrate these differential call rates using single-marker simulations. We show that call rates using the two modes of PennCNV also differ between parents-offspring in one multi-marker simulated dataset and two real datasets. Our results advise need for caution in use of the Joint-model calls in CNV association studies with family-based datasets.
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- 2012
5. Genetics of Alzheimer's Disease
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Debby Tsuang, Lynn M. Bekris, Chang En Yu, and Thomas D. Bird
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Genetics ,business.industry ,Medicine ,Disease ,business - Published
- 2010
6. Variants regulating ZBTB4 are associated with age-at-onset of Alzheimer's disease
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Nicola H. Chapman, Elizabeth E. Blue, Kati J. Buckingham, Chang En Yu, Colby T. Marvin, Timothy A. Thornton, Nan Jiang, Kathryn M. Shively, Thomas D. Bird, Ellen M. Wijsman, Eric Kernfeld, and Michael J. Bamshad
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Male ,0301 basic medicine ,Genotype ,Genetic Linkage ,Amyloid beta ,Article ,03 medical and health sciences ,Behavioral Neuroscience ,Alzheimer Disease ,Genetic linkage ,PSEN2 ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Age of Onset ,Promoter Regions, Genetic ,Gene ,Aged ,Aged, 80 and over ,Membrane Glycoproteins ,biology ,Chromosome Mapping ,Genetic Variation ,medicine.disease ,Gamma-secretase complex ,Repressor Proteins ,030104 developmental biology ,Neurology ,biology.protein ,Female ,Amyloid Precursor Protein Secretases ,Alzheimer's disease ,Amyloid precursor protein secretase ,Common disease-common variant - Abstract
The identification of novel genetic modifiers of age-at-onset of Alzheimer’s disease could advance our understanding of AD and provide novel therapeutic targets. A previous genome scan for modifiers of age-at-onset among families affected by early-onset Alzheimer’s disease caused by the PSEN2 N141I variant identified two loci with significant evidence for linkage: 1q23.3 and 17p13.2. Here, we describe the fine-mapping of these two linkage regions, and test for replication in six independent data sets. By fine-mapping these linkage signals in a single large family, we reduced the linkage regions to 11% their original size and nominated 54 candidate variants. Among the 11 variants associated with age-at-onset of Alzheimer’s disease in a larger sample of Germans from Russia, the strongest evidence implicated promoter variants influencing NCSTN on 1q23.3 and ZBTB4 on 17p13.2. The association between ZBTB4 and age-at-onset of Alzheimer’s disease was replicated by multiple variants in independent, trans-ethnic data sets. Our results demonstrate association between age-at-onset of Alzheimer’s disease and both ZBTB4 and NCSTN. ZBTB4 is a transcriptional repressor that regulates the cell cycle, including the apoptotic response to amyloid beta, while NCSTN is part of the gamma secretase complex, known to influence amyloid beta production. These genes therefore suggest important roles for amyloid beta and cell cycle pathways in age-at-onset of Alzheimer’s disease.
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- 2017
7. APOEmRNA and protein expression in postmortem brain are modulated by an extended haplotype structure
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Chang En Yu, Nichole M. Galloway, Gerard D. Schellenberg, Lynn M. Bekris, and Thomas J. Montine
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Male ,Risk ,Apolipoprotein E ,Linkage disequilibrium ,Single-nucleotide polymorphism ,Biology ,Hippocampus ,Article ,Cellular and Molecular Neuroscience ,Apolipoproteins E ,Alzheimer Disease ,Gene expression ,medicine ,Humans ,Allele ,Promoter Regions, Genetic ,Alleles ,Genetics (clinical) ,Aged ,Aged, 80 and over ,Regulation of gene expression ,Genetics ,Brain Mapping ,Reverse Transcriptase Polymerase Chain Reaction ,Haplotype ,Brain ,Middle Aged ,medicine.disease ,Psychiatry and Mental health ,Gene Expression Regulation ,Haplotypes ,Female ,lipids (amino acids, peptides, and proteins) ,Alzheimer's disease - Abstract
Currently the epsilon4 allele of the apolipoprotein E gene (APOE) is the strongest genetic risk factor for late onset Alzheimer's disease (AD). However, inheritance of the APOE epsilon4 allele is not necessary or sufficient for the development of AD. Genetic evidence suggests that multiple loci in a 70 kb region surrounding APOE are associated with AD risk. Even though these loci could represent surrogate markers in linkage disequilibrium with APOE epsilon4 allele, they could also contribute biological effects independent of the APOE epsilon4 allele. Our previous study identified multiple SNPs upstream from APOE that are associated with cerebrospinal fluid apoE levels, suggesting that a haplotype structure proximal to APOE can influence apoE expression. In this study, we examined apoE expression in human post-mortem brain (PMB), and constructed chromosome-phase-separated haplotypes of the APOE proximal region to evaluate their effect on PMB apoE expression. ApoE protein expression was found to differ among AD brain regions and to differ between AD and control hippocampus. In addition, an extended APOE proximal haplotype structure, spanning from the TOMM40 gene to the APOE promoter, may modulate apoE expression in a brain region-specific manner and may influence AD disease status. In conclusion, this haplotype-phenotype analysis of apoE expression in PMB suggests that either; (1) the cis-regulation of APOE expression levels extends far upstream of the APOE promoter or (2) an APOE epsilon4 allele independent mechanism involving the TOMM40 gene plays a role in the risk of AD.
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- 2009
8. Heterozygousparkinpoint mutations are as common in control subjects as in Parkinson's patients
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Chang En Yu, Gerard D. Schellenberg, Robert G. Keefe, Cyrus P. Zabetian, Haydeh Payami, Jennifer S. Montimurro, John G. Nutt, Lina M. Moses, Parvoneh Poorkaj, Stewart A. Factor, Dawn Moran, and Denise M. Kay
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Adult ,Male ,Heterozygote ,Genotype ,Ubiquitin-Protein Ligases ,DNA Mutational Analysis ,Biology ,Compound heterozygosity ,medicine.disease_cause ,Parkin ,Gene Frequency ,medicine ,Humans ,Point Mutation ,Genetic Predisposition to Disease ,Mutation frequency ,Allele frequency ,Aged ,Aged, 80 and over ,Genetics ,Mutation ,Point mutation ,Case-control study ,Parkinson Disease ,Middle Aged ,nervous system diseases ,Neurology ,Case-Control Studies ,Female ,Neurology (clinical) - Abstract
Objective Homozygous or compound heterozygous parkin mutations cause juvenile parkinsonism. Heterozygous parkin mutations are also found in patients with typical Parkinson's disease (PD), but it is unclear whether a single “mutation” in a patient is related to disease or is coincidental, because the mutation frequency in control subjects is unknown. We present a comprehensive sequence analysis of parkin in control subjects. Methods A total of 302 patients and 301 control subjects were sequenced, and findings were replicated in 1,260 additional patients and 1,657 control subjects. Results Thirty-four variants were detected, of which 21 were novel; 12 were polymorphisms and 22 were rare variants. Patients and control subjects did not differ in the frequency, type, or functional location of the variants. Even P437L, a common mutation thought to be pathogenic, was present in unaffected control subjects. Interpretation parkin point mutations are not exclusive to PD. The mere presence of a single point mutation in a patient, in the absence of a second mutation, should not be taken as a cause of disease unless corroborated by family data and functional studies. This study does not support the notion that heterozygous parkin sequence variants (mutations or polymorphisms) are risk factors for PD. Whether heterozygous dosage anomalies are associated with PD remains to be determined. Ann Neurol 2006
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- 2007
9. Modest evidence for linkage and possible confirmation of association between NOTCH4 and schizophrenia in a large veterans affairs cooperative study sample
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Chang En Yu, Felicitas Mena, Stephen F. Bingham, T. Keith, Paul Rundell, Debby Tsuang, Michael Boehnke, Joseph F. Collins, Andrew D. Skol, Ming T. Tsuang, David G. Weiss, Sarita Prabhudesai, Gerard D. Schellenberg, S.L. Haverstock, John R. Pepple, Clinton T. Baldwin, A.S. Menon, Stephen V. Faraone, Keith A. Young, and F. Sauter
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Genetic Markers ,Male ,Linkage disequilibrium ,Genetic Linkage ,Receptors, Cell Surface ,Schizoaffective disorder ,Biology ,Linkage Disequilibrium ,Genetic determinism ,Gene Frequency ,Genetic linkage ,Proto-Oncogene Proteins ,medicine ,Humans ,Allele ,Receptor, Notch4 ,Veterans Affairs ,Allele frequency ,Alleles ,Genetics (clinical) ,Family Health ,Genetics ,Receptors, Notch ,Haplotype ,medicine.disease ,Haplotypes ,Schizophrenia ,Female ,Lod Score - Abstract
Wei and Hemmings [2000: Nat Genet 25:376-377], using 80 British parent-offspring trios, identified a number of NOTCH4 variants and haplotypes that showed statistically significant evidence of association to schizophrenia. Specifically, the 10 repeat allele of a (CTG)(n) marker and the 8 repeat allele of a (TAA)(n) marker demonstrated excess transmission to affected individuals; SNP21 and haplotypes SNP2-(CTG)(n) and SNP12-SNP2-(CTG)(n) also showed significant associations. In an attempt to replicate these findings, we tested for linkage and association between the same five markers used by Wei and Hemmings in 166 families collected from a multi-center study conducted by the Department of Veterans Affairs (DVA) Cooperative Study Program (CSP). The families include 392 affected subjects (schizophrenia or schizoaffective disorder, depressed) and 216 affected sibling pairs. The families represent a mix of European Americans (n = 62, 37%), African Americans (n = 60, 36%), and racially mixed or other races (n = 44, 27%). We identified moderate evidence for linkage in the pooled race sample (LOD = 1.25) and found excess transmission of the 8 (P = 0.06) and 13 (P = 0.04) repeat alleles of the (TAA)(n) marker to African American schizophrenic subjects. The 8 and 13 repeat alleles were previously identified to be positively associated with schizophrenia by Wei and Hemmings [2000: Nat Genet 25:376-377] and Sklar et al. [2001: Nat Genet 28:126-128], respectively.
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- 2003
10. P4‐377: A TOMM40 SNP IN APOE E4 NON‐CARRIERS INCREASES RISK FOR MULTIPLE TYPES OF DEMENTIA
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Eliezer Masliah, Eric B. Larson, Peter T. Nelson, John Q. Trojanowski, Jeffrey Kaye, Paul K. Crane, Daniel Weintraub, Lynn M. Bekris, Debby W. Tsuang, Gerard D. Schellenberg, Douglas Galasko, Julie A. Schneider, James B. Leverenz, Ignacio F. Mata, Thomas J. Montine, Walter Kulkull, Alice Chen-Plotkin, Chang En Yu, Patricia L. Kramer, Oscar L. Lopez, Dora Yearout, Randy Woltjer, Gregory A. Jicha, David A. Bennett, R. L. Hamilton, Cyrus P. Zabetian, Aron S. Buchman, Joseph F. Quinn, Kathryn A. Chung, Stennis Watson, and Karen L. Edwards
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biology ,Interneuron ,Epidemiology ,Health Policy ,Striatum ,Nucleus accumbens ,Medium spiny neuron ,Calbindin ,Cell biology ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,medicine.anatomical_structure ,nervous system ,Developmental Neuroscience ,Dopamine receptor D2 ,biology.protein ,medicine ,GABAergic ,Neurology (clinical) ,Geriatrics and Gerontology ,Parvalbumin - Abstract
tion of 5-HT6 receptor mRNA expression by in situ hybridization we applied theQuantiGeneViewRNAplatform fromAffymetrix.We usedMultiplex analysis to study co-expression of a range of neuronal genes. Frozen sections throughout the brains from male Sprague Dawley rats were hybridized for 5HT6 receptors. Following total mapping, 5-HT6 receptor mRNAvisualization was combined with probes for a range of neurotransmitters or interneuron markers. The sectins were analyzed by bright field and fluorescent microscopy. Results: Detection of target genes was both sensitive and specific. 5-HT6 receptor mRNA was expressed exclusively in neurons. The highest expression levelwas detected inmedium spiny neurons in caudate putamen and in nucleus accumbens, and in the olfactory tubercle. The striatal neurons also expressed GAD67, calbindin and D1/D2 receptors. 5-HT6 mRNA was moderately expressed in hippocampus and throughout cortical regions. These neurons co-expressed the glutamatergic marker vGluT1. Furthermore, weak to moderate expression of cholecystokinin and calbindin mRNAwas detecetd in 5-HT6-receptor-positive cortical and hippocampal neurons. The majority of GAD67positive GABAergic interneurons (in cortex, hippocampus, striatum) did not express 5-HT6 receptor mRNA. However, a weak to moderate signal for 5HT6 receptors was present in a subset of calbindinand calretinin-positive GABAergic interneurons. 5-HT6 receptors did not co-localizewith parvalbumin in forebrain structures. 5-HT6 receptor mRNAwas not expressed in serotonergic, dopaminergic or cholinergic neurons, nor was the receptor co-expressed with somatostatin, VIP or NPY. Conclusions: 5-HT6 receptor mRNA is strongly expressed in GABAergic medium spiny neurons and moderately expressed in glutamatergic neurons. A subset of calretininand calbindin-positive GABAergic interneurons express 5-HT6 receptor mRNA. The present data provide new insights to interpret the mechanism of 5-HT6 receptor signalling.
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- 2014
11. P3–014: A TOMM40 SNP in APOE‐ε4 noncarriers increases risk for multiple types of dementia
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Lynn Bekris, Debby Tsuang, James Leverenz, Chang‐En Yu, Oscar Lopez, Ronald Hamilton, David Bennett, Eric Larson, Paul Crane, Jeffrey Kaye, John Trojanowski, Aron Buchman, Patricia Kramer, Randy Woltjer, Julie Schneider, Daniel Weintraub, Alice Chen‐Plotkin, Peter Nelson, Gregory Jicha, Gerard Schellenberg, Walter Kulkull, Stennis Watson, Douglas Galasko, Eliezer Masliah, Joseph Quinn, Kathryn Chung, Dora Yearout, Ignacio Mata, Karen Edwards, Thomas Montine, and Cyrus Zabetian
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Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2013
12. Apolipoprotein E genotypes in Parkinson's disease with and without dementia
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William C. Koller, Sander L. Glatt, Jean P. Hubble, Anthony Paolo, Alexander I. Tröster, Karen Schmidt, Annette Karst, Michael S. Handler, Rebecca T. Horvat, Coleman Martin, Ellen M. Wijsman, Chang-En Yu, and Gerard D. Schellenberg
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Apolipoprotein E ,medicine.medical_specialty ,Pathology ,education.field_of_study ,Parkinson's disease ,business.industry ,Population ,medicine.disease ,Central nervous system disease ,Neurology ,Internal medicine ,mental disorders ,medicine ,Dementia ,Neurology (clinical) ,Allele ,Age of onset ,education ,business ,Allele frequency - Abstract
The apolipoprotein E gene (Apo E) type 4 allele is a genetic risk factor influencing the development and age of onset of Alzheimer's disease. Because Parkinson's disease shares many characteristics of Alzheimer's disease, we studied the frequencies of Apo E genotypes in a cohort of 52 Parkinson's disease patients with dementia and 61 patients without dementia. Dementia was determined per National Institute of Neurological and Communicative Disorders and Stroke criteria and Mattis Dementia Rating Scale (DRS) 132. Apo E genotype and allele frequencies did not differ between demented and nondemented parkinsonian patients. Neither group's genotype and allele frequencies differed from that of a nondemented population of 78 controls. We conclude that the Apo E epsilon 4 allele influences neither the development of Parkinson's disease nor the dementia associated with Parkinson's disease.
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- 1995
13. P4‐118: Tau phosphorylation pathway genes and cerebrospinal fluid tau levels in Alzheimer's disease
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Chang En Yu, Ge Li, Franziska Lutz, James B. Leverenz, Lynn M. Bekris, Joseph F. Quinn, Elaine R. Peskind, Steven P. Millard, Debby Tsuang, Martin R. Farlow, Douglas Galasko, and Jeffrey Kaye
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medicine.medical_specialty ,Epidemiology ,Kinase ,Health Policy ,Phosphatase ,Single-nucleotide polymorphism ,Biology ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,FYN ,Cerebrospinal fluid ,Endocrinology ,Developmental Neuroscience ,Regulatory sequence ,Internal medicine ,mental disorders ,medicine ,Phosphorylation ,Neurology (clinical) ,Geriatrics and Gerontology ,Gene - Abstract
Alzheimer’s disease (AD) is characterized by the presence in the brain of amyloid plaques, consisting predominately of the amyloid β peptide (Aβ), and neurofibrillary tangles, consisting primarily of tau. Hyper-phosphorylated-tau (p-tau) contributes to neuronal damage, and both p-tau and total-tau (t-tau) levels are elevated in AD cerebrospinal fluid (CSF) compared to cognitively normal controls. Our hypothesis was that increased ratios of CSF phosphorylated-tau levels relative to total-tau levels correlate with regulatory region genetic variation of kinase or phosphatase genes biologically associated with the phosphorylation status of tau. Eighteen SNPs located within 5′ and 3′ regions of 5 kinase and 4 phosphatase genes, as well as two SNPs within regulatory regions of the MAPT gene were chosen for this analysis. The study sample consisted of 101 AD patients and 169 cognitively normal controls. Rs7768046 in the FYN kinase gene and rs913275 in the PPP2R4 phosphatase gene were both associated with CSF p-tau and t-tau levels in AD. These SNPs were also differentially associated with either CSF t-tau (rs7768046) or CSF p-tau (rs913275) relative to t-tau levels in AD compared to controls. These results suggest that rs7768046 and rs913275 both influence CSF tau levels in an AD-associated manner.
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- 2012
14. P1‐288: Is the Arg5His MAPT variant pathogenic for dementia and motor neuron disease?
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James Leverenz, Thomas Bird, Malia Rumbaugh, Chang‐en Yu, Carlos Cruchaga, Ellen Steinbart, and John Ravits
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Epidemiology ,Health Policy ,Disease ,Motor neuron ,Biology ,medicine.disease ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,medicine.anatomical_structure ,Developmental Neuroscience ,medicine ,Dementia ,Neurology (clinical) ,Geriatrics and Gerontology ,Neuroscience - Published
- 2011
15. P1‐212: Alzheimer's Disease Hippocampus Micro‐RNA Expression
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Lynn M. Bekris and Chang En Yu
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Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,microRNA ,Hippocampus ,Neurology (clinical) ,Disease ,Geriatrics and Gerontology ,Biology ,Cell biology - Published
- 2011
16. P1‐245: TOMM40 Poly‐T Length Variant and Age‐At‐Onset in Familial AD Caused by PSEN1 and PSEN2 Mutation
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Gail Li, Chang En Yu, Ellen J. Steinbart, Lynn M. Bekris, and Thomas D. Bird
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Mutation ,biology ,Epidemiology ,Endosome ,Chemistry ,Health Policy ,Phosphatase ,Regulator ,Endocytosis ,medicine.disease_cause ,Clathrin ,Synaptojanin-1 ,SYNJ1 Gene ,Cell biology ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,biology.protein ,medicine ,Neurology (clinical) ,Geriatrics and Gerontology - Abstract
overexpressed in LCL fromDS individuals. SYNJ1 gene codes for the phosphoinositide phosphatase synaptojanin 1 protein, a key regulator of the signalling phospholipids phosphatidylinositol-4,5-biphosphate [PtdIns (4,5) P2]. PtdIns (4,5)P2 has been shown to interact with clathrin coated pits and to regulate endocytosis. Finally, we demonstrate that synaptojanin 1 overexpression by itself, in neuroblastoma cells and TgSYNJ1 mice, leads to the enlargement of early endosomes.
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- 2011
17. P4‐027: Cerebrocerebellar Hypometablism Associated With Repetitive Blast Exposure Mild Traumatic Brain Injury in 12 Iraq War Veterans With Persistent Post‐Concussive Symptoms
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Donna J. Cross, Murray A. Raskind, Kathleen McCraw, Kathleen F. Pagulayan, Satoshi Minoshima, Eric C. Petrie, David G. Cook, Elaine R. Peskind, Chang En Yu, David Hoff, and Kim Hart
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medicine.medical_specialty ,Iraq war ,Post-Concussive Symptoms ,Epidemiology ,Traumatic brain injury ,Health Policy ,Blast exposure ,medicine.disease ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,medicine ,Neurology (clinical) ,Geriatrics and Gerontology ,Psychology ,Psychiatry ,Clinical psychology - Published
- 2010
18. O1‐07‐06: A genome‐wide association study of progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD)
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Gerard D. Schellenberg, Günter Höglinger, Patrick Sleiman, Rosa Rademakers, Lambertus Kei, Rohan Silva, Li-San Wang, Chang-En Yu, null PSP/CBD Consortium, Peter Heutink, John Swieten, Mathew Farrer, John Hardy, Andrew Lees, Bernie Devlin, Hakon Hakonarson, Dennis W. Dickson, and Ulrich Müller
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Pathology ,medicine.medical_specialty ,Epidemiology ,business.industry ,Health Policy ,Genome-wide association study ,medicine.disease ,Progressive supranuclear palsy ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,medicine ,Corticobasal degeneration ,Neurology (clinical) ,Geriatrics and Gerontology ,business - Published
- 2010
19. P1‐059: Can late‐onset familial Alzheimer's disease be an autosomal dominant Mendelian disorder?
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Chang En Yu, Ellen J. Steinbart, James B. Leverenz, Kate Nickel, Malia Rumbaugh, and Thomas D. Bird
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Genetics ,Epidemiology ,business.industry ,Health Policy ,Late onset ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,symbols.namesake ,Developmental Neuroscience ,Familial Alzheimer's disease ,Mendelian inheritance ,symbols ,Medicine ,Neurology (clinical) ,Geriatrics and Gerontology ,business - Published
- 2010
20. Evidence for three loci modifying age-at-onset of Alzheimer's disease in early-onsetPSEN2families
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Thomas D. Bird, Ellen M. Wijsman, Gerard D. Schellenberg, Chang En Yu, Elizabeth E. Marchani, Ellen J. Steinbart, and Elisabeth A. Rosenthal
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Adult ,Genetic Markers ,Candidate gene ,Genetic Linkage ,Quantitative Trait Loci ,Locus (genetics) ,Single-nucleotide polymorphism ,Biology ,Quantitative trait locus ,White People ,Article ,Cellular and Molecular Neuroscience ,Alzheimer Disease ,Genetic linkage ,Chromosome Segregation ,Germany ,Presenilin-2 ,Chromosomes, Human ,Humans ,Family ,Age of Onset ,Genetics (clinical) ,Aged ,Aged, 80 and over ,Genetics ,Genome, Human ,Middle Aged ,Major gene ,Complete linkage ,Psychiatry and Mental health ,Genetic Loci ,Age of onset - Abstract
Families with early-onset Alzheimer’s disease (AD) sharing a single PSEN2 mutation exhibit a wide range of age-at-onset, suggesting that modifier loci segregate within these families. While APOE is known to be an age-at-onset modifier, it does not explain all of this variation. We performed a genome scan within nine such families for loci influencing age-at-onset, while simultaneously controlling for variation in the primary PSEN2 mutation (N141I) and APOE. We found significant evidence of linkage between age-at-onset and chromosome 1q23.3 (P < 0.001) when analysis included all families, and to chromosomes 1q23.3 (P < 0.001), 17p13.2 (P = 0.0002), 7q33 (P = 0.017), and 11p14.2 (P = 0.017) in a single large pedigree. Simultaneous analysis of these four chromosomes maintained strong evidence of linkage to chromosomes 1q23.3 and 17p13.2 when all families were analyzed, and to chromosomes 1q23.3, 7q33, and 17p13.2 within the same single pedigree. Inclusion of major gene covariates proved essential to detect these linkage signals, as all linkage signals dissipated when PSEN2 and APOE were excluded from the model. The four chromosomal regions with evidence of linkage all coincide with previous linkage signals, associated SNPs, and/or candidate genes identified in independent AD study populations. This study establishes several candidate regions for further analysis and is consistent with an oligogenic model of AD risk and age-at-onset. More generally, this study also demonstrates the value of searching for modifier loci in existing datasets previously used to identify primary causal variants for complex disease traits.
- Published
- 2010
21. O2–01–01: A natural a natural antisense gene regulates MAPT expression
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James B. Leverenz, Chang En Yu, Ian D'Souza, Pamela J. McMillan, and Gerard D. Schellenberg
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Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2006
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