12 results on '"Weichert, Anna"'
Search Results
2. MicroRNA Expression Levels Are Altered in the Cerebrospinal Fluid of Patients with Young-Onset Alzheimer’s Disease
- Author
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McKeever, Paul M, Schneider, Raphael, Taghdiri, Foad, Weichert, Anna, Multani, Namita, Brown, Robert A, Boxer, Adam L, Karydas, Anna, Miller, Bruce, Robertson, Janice, and Tartaglia, Maria Carmela
- Subjects
Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Genetics ,Dementia ,Biotechnology ,Brain Disorders ,Neurosciences ,Neurodegenerative ,Acquired Cognitive Impairment ,Alzheimer's Disease ,Aging ,Prevention ,Detection ,screening and diagnosis ,Aetiology ,2.1 Biological and endogenous factors ,4.1 Discovery and preclinical testing of markers and technologies ,Neurological ,Age of Onset ,Aged ,Alzheimer Disease ,Case-Control Studies ,Exosomes ,Female ,Gene Expression Profiling ,Gene Ontology ,Gyrus Cinguli ,Humans ,Male ,MicroRNAs ,Middle Aged ,Reproducibility of Results ,Alzheimer's disease ,Young-onset ,Cerebrospinal fluid ,MicroRNA ,Alzheimer’s disease ,Psychology ,Cognitive Sciences ,Neurology & Neurosurgery - Abstract
Clinical diagnosis of Alzheimer's disease (AD) prior to the age of 65 years is classified as young-onset (YOAD), whereas diagnosis after the age of 65 years is considered late-onset (LOAD). Although rare autosomal mutations more commonly associate with YOAD, most YOAD and LOAD cases are sporadic. YOAD and LOAD share amyloid and tau pathology, but many YOAD patients show increased disease severity and rate of progression. The current study examined the microRNA (miRNA) expression profile from exosomes isolated from the cerebrospinal fluid (CSF) of YOAD patients with biomarker-confirmed AD. Results uncovered miR-16-5p, miR-125b-5p, miR-451a, and miR-605-5p as differentially expressed in the CSF-derived exosomes of YOAD patients when compared with healthy controls (HC). In a cohort of LOAD patients, miR-125b-5p, miR-451a, and miR-605-5p were similarly altered in expression, but miR-16-5p showed similar expression to control. Analysis of the mRNA targets of these miRNAs revealed transcripts enriched in biological processes relevant to the post-mortem posterior cingulate cortex transcriptome in YOAD from a previously published microarray study, including those related to neuron projections, synaptic signaling, metabolism, apoptosis, and the immune system. Hence, these miRNAs represent novel targets for uncovering disease mechanisms and for biomarker development in both YOAD and LOAD.
- Published
- 2018
3. A C6orf10/LOC101929163 locus is associated with age of onset in C9orf72 carriers.
- Author
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Zhang, Ming, Ferrari, Raffaele, Tartaglia, Maria Carmela, Keith, Julia, Surace, Ezequiel I, Wolf, Uri, Sato, Christine, Grinberg, Mark, Liang, Yan, Xi, Zhengrui, Dupont, Kyle, McGoldrick, Philip, Weichert, Anna, McKeever, Paul M, Schneider, Raphael, McCorkindale, Michael D, Manzoni, Claudia, Rademakers, Rosa, Graff-Radford, Neill R, Dickson, Dennis W, Parisi, Joseph E, Boeve, Bradley F, Petersen, Ronald C, Miller, Bruce L, Seeley, William W, van Swieten, John C, van Rooij, Jeroen, Pijnenburg, Yolande, van der Zee, Julie, Van Broeckhoven, Christine, Le Ber, Isabelle, Van Deerlin, Vivianna, Suh, EunRan, Rohrer, Jonathan D, Mead, Simon, Graff, Caroline, Öijerstedt, Linn, Pickering-Brown, Stuart, Rollinson, Sara, Rossi, Giacomina, Tagliavini, Fabrizio, Brooks, William S, Dobson-Stone, Carol, Halliday, Glenda M, Hodges, John R, Piguet, Olivier, Binetti, Giuliano, Benussi, Luisa, Ghidoni, Roberta, Nacmias, Benedetta, Sorbi, Sandro, Bruni, Amalia C, Galimberti, Daniela, Scarpini, Elio, Rainero, Innocenzo, Rubino, Elisa, Clarimon, Jordi, Lleó, Alberto, Ruiz, Agustin, Hernández, Isabel, Pastor, Pau, Diez-Fairen, Monica, Borroni, Barbara, Pasquier, Florence, Deramecourt, Vincent, Lebouvier, Thibaud, Perneczky, Robert, Diehl-Schmid, Janine, Grafman, Jordan, Huey, Edward D, Mayeux, Richard, Nalls, Michael A, Hernandez, Dena, Singleton, Andrew, Momeni, Parastoo, Zeng, Zhen, Hardy, John, Robertson, Janice, Zinman, Lorne, Rogaeva, Ekaterina, and International FTD-Genomics Consortium (IFGC)
- Subjects
International FTD-Genomics Consortium ,Humans ,Amyotrophic Lateral Sclerosis ,Age of Onset ,DNA Methylation ,Gene Expression Regulation ,CpG Islands ,Genotype ,Heterozygote ,Polymorphism ,Single Nucleotide ,Aged ,Middle Aged ,Female ,Male ,Frontotemporal Dementia ,C9orf72 Protein ,C9orf72 ,genetic association ,age of onset ,amyotrophic lateral sclerosis ,frontotemporal dementia ,Polymorphism ,Single Nucleotide ,Neurology & Neurosurgery ,Medical and Health Sciences ,Psychology and Cognitive Sciences - Abstract
The G4C2-repeat expansion in C9orf72 is the most common known cause of amyotrophic lateral sclerosis and frontotemporal dementia. The high phenotypic heterogeneity of C9orf72 patients includes a wide range in age of onset, modifiers of which are largely unknown. Age of onset could be influenced by environmental and genetic factors both of which may trigger DNA methylation changes at CpG sites. We tested the hypothesis that age of onset in C9orf72 patients is associated with some common single nucleotide polymorphisms causing a gain or loss of CpG sites and thus resulting in DNA methylation alterations. Combined analyses of epigenetic and genetic data have the advantage of detecting functional variants with reduced likelihood of false negative results due to excessive correction for multiple testing in genome-wide association studies. First, we estimated the association between age of onset in C9orf72 patients (n = 46) and the DNA methylation levels at all 7603 CpG sites available on the 450 k BeadChip that are mapped to common single nucleotide polymorphisms. This was followed by a genetic association study of the discovery (n = 144) and replication (n = 187) C9orf72 cohorts. We found that age of onset was reproducibly associated with polymorphisms within a 124.7 kb linkage disequilibrium block tagged by top-significant variation, rs9357140, and containing two overlapping genes (LOC101929163 and C6orf10). A meta-analysis of all 331 C9orf72 carriers revealed that every A-allele of rs9357140 reduced hazard by 30% (P = 0.0002); and the median age of onset in AA-carriers was 6 years later than GG-carriers. In addition, we investigated a cohort of C9orf72 negative patients (n = 2634) affected by frontotemporal dementia and/or amyotrophic lateral sclerosis; and also found that the AA-genotype of rs9357140 was associated with a later age of onset (adjusted P = 0.007 for recessive model). Phenotype analyses detected significant association only in the largest subgroup of patients with frontotemporal dementia (n = 2142, adjusted P = 0.01 for recessive model). Gene expression studies of frontal cortex tissues from 25 autopsy cases affected by amyotrophic lateral sclerosis revealed that the G-allele of rs9357140 is associated with increased brain expression of LOC101929163 (a non-coding RNA) and HLA-DRB1 (involved in initiating immune responses), while the A-allele is associated with their reduced expression. Our findings suggest that carriers of the rs9357140 GG-genotype (linked to an earlier age of onset) might be more prone to be in a pro-inflammatory state (e.g. by microglia) than AA-carriers. Further, investigating the functional links within the C6orf10/LOC101929163/HLA-DRB1 pathway will be critical to better define age-dependent pathogenesis of frontotemporal dementia and amyotrophic lateral sclerosis.
- Published
- 2018
4. Mechanisms Associated with TDP-43 Neurotoxicity in ALS/FTLD
- Author
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Shenouda, Marc, Zhang, Ashley B., Weichert, Anna, Robertson, Janice, Schousboe, Arne, Series Editor, Sattler, Rita, editor, and Donnelly, Christopher J., editor
- Published
- 2018
- Full Text
- View/download PDF
5. DNA methylation age-acceleration is associated with disease duration and age at onset in C9orf72 patients
- Author
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Zhang, Ming, Tartaglia, Maria Carmela, Moreno, Danielle, Sato, Christine, McKeever, Paul, Weichert, Anna, Keith, Julia, Robertson, Janice, Zinman, Lorne, and Rogaeva, Ekaterina
- Published
- 2017
- Full Text
- View/download PDF
6. Clinical Reasoning: A 42-year-old man with unilateral leg weakness
- Author
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Schneider, Raphael, Weichert, Anna, Rogaeva, Ekaterina, Robertson, Janice, Keith, Julia, and Zinman, Lorne
- Published
- 2018
- Full Text
- View/download PDF
7. Unaffected mosaic C9orf72 case: RNA foci, dipeptide proteins, but upregulated C9orf72 expression
- Author
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McGoldrick, Philip, Zhang, Ming, van Blitterswijk, Marka, Sato, Christine, Moreno, Danielle, Xiao, Shangxi, Zhang, Ashley B., McKeever, Paul M., Weichert, Anna, Schneider, Raphael, Keith, Julia, Petrucelli, Leonard, Rademakers, Rosa, Zinman, Lorne, Robertson, Janice, and Rogaeva, Ekaterina
- Published
- 2018
- Full Text
- View/download PDF
8. A C6orf10/LOC101929163 locus is associated with age of onset in C9orf72 carriers
- Author
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Zhang, Ming, Ferrari, Raffaele, Tartaglia, Maria Carmela, Keith, Julia, Surace, Ezequiel I, Wolf, Uri, Sato, Christine, Grinberg, Mark, Liang, Yan, Xi, Zhengrui, Dupont, Kyle, McGoldrick, Philip, Weichert, Anna, McKeever, Paul M, Schneider, Raphael, McCorkindale, Michael D, Manzoni, Claudia, Rademakers, Rosa, Graff-Radford, Neill R, Dickson, Dennis W, Parisi, Joseph E, Boeve, Bradley F, Petersen, Ronald C, Miller, Bruce L, Seeley, William W, Van Swieten, John C, Van Rooij, Jeroen, Pijnenburg, Yolande, Van Der Zee, Julie, Van Broeckhoven, Christine, Le Ber, Isabelle, Van Deerlin, Vivianna, Suh, EunRan, Rohrer, Jonathan D, Mead, Simon, Graff, Caroline, Öijerstedt, Linn, Pickering-Brown, Stuart, Rollinson, Sara, Rossi, Giacomina, Tagliavini, Fabrizio, Brooks, William S, Dobson-Stone, Carol, Halliday, Glenda M, Hodges, John R, Piguet, Olivier, Binetti, Giuliano, Benussi, Luisa, Ghidoni, Roberta, Nacmias, Benedetta, Sorbi, Sandro, Bruni, Amalia C, Galimberti, Daniela, Scarpini, Elio, Rainero, Innocenzo, Rubino, Elisa, Clarimon, Jordi, Lleó, Alberto, Ruiz, Agustin, Hernández, Isabel, Pastor, Pau, Diez-Fairen, Monica, Borroni, Barbara, Pasquier, Florence, Deramecourt, Vincent, Lebouvier, Thibaud, Perneczky, Robert, Diehl-Schmid, Janine, Grafman, Jordan, Huey, Edward D, Mayeux, Richard, Nalls, Michael A, Hernandez, Dena, Singleton, Andrew, Momeni, Parastoo, Zeng, Zhen, Hardy, John, Robertson, Janice, Zinman, Lorne, Rogaeva, Ekaterina, International FTD-Genomics Consortium (IFGC), Schneider, Raphael [0000-0003-1776-2418], Manzoni, Claudia [0000-0001-5367-4023], Diez-Fairen, Monica [0000-0003-1882-0309], and Apollo - University of Cambridge Repository
- Subjects
Male ,Aging ,amyotrophic lateral sclerosis ,Heterozygote ,genetic association ,Genotype ,Neurodegenerative ,Medical and Health Sciences ,frontotemporal dementia ,Polymorphism, Single Nucleotide ,Rare Diseases ,age of onset ,Clinical Research ,C9orf72 ,Acquired Cognitive Impairment ,Genetics ,2.1 Biological and endogenous factors ,Humans ,Polymorphism ,Aetiology ,Age of Onset ,Aged ,Neurology & Neurosurgery ,C9orf72 Protein ,International FTD-Genomics Consortium ,Human Genome ,Psychology and Cognitive Sciences ,Amyotrophic Lateral Sclerosis ,Neurosciences ,Single Nucleotide ,DNA Methylation ,Middle Aged ,Brain Disorders ,Gene Expression Regulation ,Frontotemporal Dementia ,Neurological ,Dementia ,CpG Islands ,Female ,ALS ,Biotechnology - Abstract
The G4C2-repeat expansion in C9orf72 is the most common known cause of amyotrophic lateral sclerosis and frontotemporal dementia. The high phenotypic heterogeneity of C9orf72 patients includes a wide range in age of onset, modifiers of which are largely unknown. Age of onset could be influenced by environmental and genetic factors both of which may trigger DNA methylation changes at CpG sites. We tested the hypothesis that age of onset in C9orf72 patients is associated with some common single nucleotide polymorphisms causing a gain or loss of CpG sites and thus resulting in DNA methylation alterations. Combined analyses of epigenetic and genetic data have the advantage of detecting functional variants with reduced likelihood of false negative results due to excessive correction for multiple testing in genome-wide association studies. First, we estimated the association between age of onset in C9orf72 patients (n = 46) and the DNA methylation levels at all 7603 CpG sites available on the 450 k BeadChip that are mapped to common single nucleotide polymorphisms. This was followed by a genetic association study of the discovery (n = 144) and replication (n = 187) C9orf72 cohorts. We found that age of onset was reproducibly associated with polymorphisms within a 124.7 kb linkage disequilibrium block tagged by top-significant variation, rs9357140, and containing two overlapping genes (LOC101929163 and C6orf10). A meta-analysis of all 331 C9orf72 carriers revealed that every A-allele of rs9357140 reduced hazard by 30% (P = 0.0002); and the median age of onset in AA-carriers was 6 years later than GG-carriers. In addition, we investigated a cohort of C9orf72 negative patients (n = 2634) affected by frontotemporal dementia and/or amyotrophic lateral sclerosis; and also found that the AA-genotype of rs9357140 was associated with a later age of onset (adjusted P = 0.007 for recessive model). Phenotype analyses detected significant association only in the largest subgroup of patients with frontotemporal dementia (n = 2142, adjusted P = 0.01 for recessive model). Gene expression studies of frontal cortex tissues from 25 autopsy cases affected by amyotrophic lateral sclerosis revealed that the G-allele of rs9357140 is associated with increased brain expression of LOC101929163 (a non-coding RNA) and HLA-DRB1 (involved in initiating immune responses), while the A-allele is associated with their reduced expression. Our findings suggest that carriers of the rs9357140 GG-genotype (linked to an earlier age of onset) might be more prone to be in a pro-inflammatory state (e.g. by microglia) than AA-carriers. Further, investigating the functional links within the C6orf10/LOC101929163/HLA-DRB1 pathway will be critical to better define age-dependent pathogenesis of frontotemporal dementia and amyotrophic lateral sclerosis.
- Published
- 2019
- Full Text
- View/download PDF
9. Unaffected mosaic C9orf72 case
- Author
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McGoldrick, Philip, primary, Zhang, Ming, additional, van Blitterswijk, Marka, additional, Sato, Christine, additional, Moreno, Danielle, additional, Xiao, Shangxi, additional, Zhang, Ashley B., additional, McKeever, Paul M., additional, Weichert, Anna, additional, Schneider, Raphael, additional, Keith, Julia, additional, Petrucelli, Leonard, additional, Rademakers, Rosa, additional, Zinman, Lorne, additional, Robertson, Janice, additional, and Rogaeva, Ekaterina, additional
- Published
- 2017
- Full Text
- View/download PDF
10. Der Einfluss einer wildtypischen SOD1-Untereinheit auf Konformation und Stabilität mutanter SOD1-Heterodimere
- Author
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Weichert, Anna
- Subjects
570 Biowissenschaften ,570 Life sciences - Published
- 2013
- Full Text
- View/download PDF
11. Unaffected mosaic case: RNA foci, dipeptide proteins, but upregulated C9orf72 expression.
- Author
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McGoldrick, Philip, Ming Zhang, van Blitterswijk, Marka, Sato, Christine, Moreno, Danielle, Shangxi Xiao, Zhang, Ashley B., McKeever, Paul M., Weichert, Anna, Schneider, Raphael, Keith, Julia, Petrucelli, Leonard, Rademakers, Rosa, Zinman, Lorne, Robertson, Janice, Rogaeva, Ekaterina, Zhang, Ming, and Xiao, Shangxi
- Published
- 2018
- Full Text
- View/download PDF
12. Wild-type Cu/Zn superoxide dismutase stabilizes mutant variants by heterodimerization
- Author
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Weichert, Anna, primary, Besemer, Anna S., additional, Liebl, Martina, additional, Hellmann, Nadja, additional, Koziollek-Drechsler, Ingrid, additional, Ip, Philbert, additional, Decker, Heinz, additional, Robertson, Janice, additional, Chakrabartty, Avijit, additional, Behl, Christian, additional, and Clement, Albrecht M., additional
- Published
- 2014
- Full Text
- View/download PDF
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