Format

Send to

Choose Destination
EMBO Mol Med. 2018 Dec;10(12). pii: e9712. doi: 10.15252/emmm.201809712.

CSF progranulin increases in the course of Alzheimer's disease and is associated with sTREM2, neurodegeneration and cognitive decline.

Author information

1
Chair of Metabolic Biochemistry, Biomedical Center (BMC), Faculty of Medicine, Ludwig-Maximilians-Universität München, Munich, Germany msuarez@barcelonabeta.org christian.haass@mail03.med.uni-muenchen.de.
2
German Center for Neurodegenerative Diseases (DZNE) Munich, Munich, Germany.
3
Chair of Metabolic Biochemistry, Biomedical Center (BMC), Faculty of Medicine, Ludwig-Maximilians-Universität München, Munich, Germany.
4
Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany.
5
Department of Neurology, Institut d'Investigacions Biomèdiques, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain.
6
Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
7
Izmir International Biomedicine and Genome Institute Dokuz, Eylul University, Izmir, Turkey.
8
Department of Neuroscience, Institute of Health Sciences, Dokuz Eylul University, Izmir, Turkey.
9
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
10
Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
11
Hope Center for Neurological Disorders, Washington University in St. Louis, St. Louis, MO, USA.
12
Knight Alzheimer's Disease Research Center, Washington University in St. Louis, St. Louis, MO, USA.
13
Department of Neurology, Ludwig-Maximilians-Universität München, Munich, Germany.
14
German Center for Neurodegenerative Diseases (DZNE) Tübingen, Tübingen, Germany.
15
Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
16
The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Vic., Australia.
17
Dementia Research Centre, UCL Institute of Neurology, London, UK.
18
Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
19
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
20
Center for Neurodegenerative Disease Research, Institute on Aging, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
21
University of California at San Francisco, San Francisco, CA, USA.

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.

KEYWORDS:

Alzheimer's disease; TREM2; biomarker; microglia; progranulin

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center