EMBO Molecular Medicine (Nov 2018)
CSF progranulin increases in the course of Alzheimer's disease and is associated with sTREM2, neurodegeneration and cognitive decline
- 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
Affiliations
- Marc Suárez‐Calvet
- Chair of Metabolic Biochemistry, Biomedical Center (BMC), Faculty of Medicine, Ludwig‐Maximilians‐Universität München
- Anja Capell
- Chair of Metabolic Biochemistry, Biomedical Center (BMC), Faculty of Medicine, Ludwig‐Maximilians‐Universität München
- Miguel Ángel Araque Caballero
- Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig‐Maximilians‐Universität München
- Estrella Morenas‐Rodríguez
- Chair of Metabolic Biochemistry, Biomedical Center (BMC), Faculty of Medicine, Ludwig‐Maximilians‐Universität München
- Katrin Fellerer
- Chair of Metabolic Biochemistry, Biomedical Center (BMC), Faculty of Medicine, Ludwig‐Maximilians‐Universität München
- Nicolai Franzmeier
- Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig‐Maximilians‐Universität München
- Gernot Kleinberger
- Chair of Metabolic Biochemistry, Biomedical Center (BMC), Faculty of Medicine, Ludwig‐Maximilians‐Universität München
- Erden Eren
- Chair of Metabolic Biochemistry, Biomedical Center (BMC), Faculty of Medicine, Ludwig‐Maximilians‐Universität München
- Yuetiva Deming
- Department of Psychiatry, Washington University School of Medicine
- Laura Piccio
- Department of Neurology, Washington University School of Medicine
- Celeste M Karch
- Department of Psychiatry, Washington University School of Medicine
- Carlos Cruchaga
- Department of Psychiatry, Washington University School of Medicine
- Katrina Paumier
- Department of Neurology, Washington University School of Medicine
- Randall J Bateman
- Department of Neurology, Washington University School of Medicine
- Anne M Fagan
- Department of Neurology, Washington University School of Medicine
- John C Morris
- Department of Neurology, Washington University School of Medicine
- Johannes Levin
- German Center for Neurodegenerative Diseases (DZNE) Munich
- Adrian Danek
- Department of Neurology, Ludwig‐Maximilians‐Universität München
- Mathias Jucker
- German Center for Neurodegenerative Diseases (DZNE) Tübingen
- Colin L Masters
- The Florey Institute of Neuroscience and Mental Health, University of Melbourne
- Martin N Rossor
- Dementia Research Centre, UCL Institute of Neurology
- John M Ringman
- Department of Neurology, Keck School of Medicine, University of Southern California
- Leslie M Shaw
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
- John Q Trojanowski
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
- Michael Weiner
- University of California at San Francisco
- Michael Ewers
- Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig‐Maximilians‐Universität München
- Christian Haass
- Chair of Metabolic Biochemistry, Biomedical Center (BMC), Faculty of Medicine, Ludwig‐Maximilians‐Universität München
- the Dominantly Inherited Alzheimer Network
- the Alzheimer's Disease Neuroimaging Initiative
- DOI
- https://doi.org/10.15252/emmm.201809712
- Journal volume & issue
-
Vol. 10,
no. 12
pp. 1 – 21
Abstract
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.
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