CSF progranulin increases in the course of Alzheimer's disease and is associated with sTREM2, neurodegeneration and cognitive decline
Abstract Progranulin (PGRN) is predominantly expressed by microglia in the brain, and genetic and experimental evidence suggests a critical role in Alzheimer's disease (AD). We asked whether PGRN expression is changed in a disease severity‐specific manner in AD. We measured PGRN in cerebrospina...
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| Format: | Article |
| Language: | English |
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Springer Nature
2018-11-01
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| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.201809712 |
| _version_ | 1827015096216322048 |
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| author | Marc Suárez‐Calvet Anja Capell Miguel Ángel Araque Caballero Estrella Morenas‐Rodríguez Katrin Fellerer Nicolai Franzmeier Gernot Kleinberger Erden Eren Yuetiva Deming Laura Piccio Celeste M Karch Carlos Cruchaga Katrina Paumier Randall J Bateman Anne M Fagan John C Morris Johannes Levin Adrian Danek Mathias Jucker Colin L Masters Martin N Rossor John M Ringman Leslie M Shaw John Q Trojanowski Michael Weiner Michael Ewers Christian Haass the Dominantly Inherited Alzheimer Network the Alzheimer's Disease Neuroimaging Initiative |
| author_facet | Marc Suárez‐Calvet Anja Capell Miguel Ángel Araque Caballero Estrella Morenas‐Rodríguez Katrin Fellerer Nicolai Franzmeier Gernot Kleinberger Erden Eren Yuetiva Deming Laura Piccio Celeste M Karch Carlos Cruchaga Katrina Paumier Randall J Bateman Anne M Fagan John C Morris Johannes Levin Adrian Danek Mathias Jucker Colin L Masters Martin N Rossor John M Ringman Leslie M Shaw John Q Trojanowski Michael Weiner Michael Ewers Christian Haass the Dominantly Inherited Alzheimer Network the Alzheimer's Disease Neuroimaging Initiative |
| author_sort | Marc Suárez‐Calvet |
| collection | DOAJ |
| description | Abstract Progranulin (PGRN) is predominantly expressed by microglia in the brain, and genetic and experimental evidence suggests a critical role in Alzheimer's disease (AD). We asked whether PGRN expression is changed in a disease severity‐specific manner in AD. We measured PGRN in cerebrospinal fluid (CSF) in two of the best‐characterized AD patient cohorts, namely the Dominant Inherited Alzheimer's Disease Network (DIAN) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). In carriers of AD causing dominant mutations, cross‐sectionally assessed CSF PGRN increased over the course of the disease and significantly differed from non‐carriers 10 years before the expected symptom onset. In late‐onset AD, higher CSF PGRN was associated with more advanced disease stages and cognitive impairment. Higher CSF PGRN was associated with higher CSF soluble TREM2 (triggering receptor expressed on myeloid cells 2) only when there was underlying pathology, but not in controls. In conclusion, we demonstrate that, although CSF PGRN is not a diagnostic biomarker for AD, it may together with sTREM2 reflect microglial activation during the disease. |
| first_indexed | 2024-03-07T17:36:44Z |
| format | Article |
| id | doaj.art-1fe5940f23884dd28924de1e2c522e1d |
| institution | Directory Open Access Journal |
| issn | 1757-4676 1757-4684 |
| language | English |
| last_indexed | 2025-02-18T14:17:39Z |
| publishDate | 2018-11-01 |
| publisher | Springer Nature |
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| series | EMBO Molecular Medicine |
| spelling | doaj.art-1fe5940f23884dd28924de1e2c522e1d2024-10-28T08:56:58ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842018-11-01101212110.15252/emmm.201809712CSF progranulin increases in the course of Alzheimer's disease and is associated with sTREM2, neurodegeneration and cognitive declineMarc Suárez‐Calvet0Anja Capell1Miguel Ángel Araque Caballero2Estrella Morenas‐Rodríguez3Katrin Fellerer4Nicolai Franzmeier5Gernot Kleinberger6Erden Eren7Yuetiva Deming8Laura Piccio9Celeste M Karch10Carlos Cruchaga11Katrina Paumier12Randall J Bateman13Anne M Fagan14John C Morris15Johannes Levin16Adrian Danek17Mathias Jucker18Colin L Masters19Martin N Rossor20John M Ringman21Leslie M Shaw22John Q Trojanowski23Michael Weiner24Michael Ewers25Christian Haass26the Dominantly Inherited Alzheimer Networkthe Alzheimer's Disease Neuroimaging InitiativeChair of Metabolic Biochemistry, Biomedical Center (BMC), Faculty of Medicine, Ludwig‐Maximilians‐Universität MünchenChair of Metabolic Biochemistry, Biomedical Center (BMC), Faculty of Medicine, Ludwig‐Maximilians‐Universität MünchenInstitute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig‐Maximilians‐Universität MünchenChair of Metabolic Biochemistry, Biomedical Center (BMC), Faculty of Medicine, Ludwig‐Maximilians‐Universität MünchenChair of Metabolic Biochemistry, Biomedical Center (BMC), Faculty of Medicine, Ludwig‐Maximilians‐Universität MünchenInstitute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig‐Maximilians‐Universität MünchenChair of Metabolic Biochemistry, Biomedical Center (BMC), Faculty of Medicine, Ludwig‐Maximilians‐Universität MünchenChair of Metabolic Biochemistry, Biomedical Center (BMC), Faculty of Medicine, Ludwig‐Maximilians‐Universität MünchenDepartment of Psychiatry, Washington University School of MedicineDepartment of Neurology, Washington University School of MedicineDepartment of Psychiatry, Washington University School of MedicineDepartment of Psychiatry, Washington University School of MedicineDepartment of Neurology, Washington University School of MedicineDepartment of Neurology, Washington University School of MedicineDepartment of Neurology, Washington University School of MedicineDepartment of Neurology, Washington University School of MedicineGerman Center for Neurodegenerative Diseases (DZNE) MunichDepartment of Neurology, Ludwig‐Maximilians‐Universität MünchenGerman Center for Neurodegenerative Diseases (DZNE) TübingenThe Florey Institute of Neuroscience and Mental Health, University of MelbourneDementia Research Centre, UCL Institute of NeurologyDepartment of Neurology, Keck School of Medicine, University of Southern CaliforniaDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of PennsylvaniaDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of PennsylvaniaUniversity of California at San FranciscoInstitute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig‐Maximilians‐Universität MünchenChair of Metabolic Biochemistry, Biomedical Center (BMC), Faculty of Medicine, Ludwig‐Maximilians‐Universität MünchenAbstract Progranulin (PGRN) is predominantly expressed by microglia in the brain, and genetic and experimental evidence suggests a critical role in Alzheimer's disease (AD). We asked whether PGRN expression is changed in a disease severity‐specific manner in AD. We measured PGRN in cerebrospinal fluid (CSF) in two of the best‐characterized AD patient cohorts, namely the Dominant Inherited Alzheimer's Disease Network (DIAN) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). In carriers of AD causing dominant mutations, cross‐sectionally assessed CSF PGRN increased over the course of the disease and significantly differed from non‐carriers 10 years before the expected symptom onset. In late‐onset AD, higher CSF PGRN was associated with more advanced disease stages and cognitive impairment. Higher CSF PGRN was associated with higher CSF soluble TREM2 (triggering receptor expressed on myeloid cells 2) only when there was underlying pathology, but not in controls. In conclusion, we demonstrate that, although CSF PGRN is not a diagnostic biomarker for AD, it may together with sTREM2 reflect microglial activation during the disease.https://doi.org/10.15252/emmm.201809712Alzheimer's diseasebiomarkermicrogliaprogranulinTREM2 |
| spellingShingle | Marc Suárez‐Calvet Anja Capell Miguel Ángel Araque Caballero Estrella Morenas‐Rodríguez Katrin Fellerer Nicolai Franzmeier Gernot Kleinberger Erden Eren Yuetiva Deming Laura Piccio Celeste M Karch Carlos Cruchaga Katrina Paumier Randall J Bateman Anne M Fagan John C Morris Johannes Levin Adrian Danek Mathias Jucker Colin L Masters Martin N Rossor John M Ringman Leslie M Shaw John Q Trojanowski Michael Weiner Michael Ewers Christian Haass the Dominantly Inherited Alzheimer Network the Alzheimer's Disease Neuroimaging Initiative CSF progranulin increases in the course of Alzheimer's disease and is associated with sTREM2, neurodegeneration and cognitive decline EMBO Molecular Medicine Alzheimer's disease biomarker microglia progranulin TREM2 |
| title | CSF progranulin increases in the course of Alzheimer's disease and is associated with sTREM2, neurodegeneration and cognitive decline |
| title_full | CSF progranulin increases in the course of Alzheimer's disease and is associated with sTREM2, neurodegeneration and cognitive decline |
| title_fullStr | CSF progranulin increases in the course of Alzheimer's disease and is associated with sTREM2, neurodegeneration and cognitive decline |
| title_full_unstemmed | CSF progranulin increases in the course of Alzheimer's disease and is associated with sTREM2, neurodegeneration and cognitive decline |
| title_short | CSF progranulin increases in the course of Alzheimer's disease and is associated with sTREM2, neurodegeneration and cognitive decline |
| title_sort | csf progranulin increases in the course of alzheimer s disease and is associated with strem2 neurodegeneration and cognitive decline |
| topic | Alzheimer's disease biomarker microglia progranulin TREM2 |
| url | https://doi.org/10.15252/emmm.201809712 |
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