Biomarkers & Diagnostic Imaging
- Soluble stroma‐related biomarkers of pancreatic cancer
- Andrea Resovi1,†,
- Maria Rosa Bani1,†,
- Luca Porcu2,
- Alessia Anastasia1,
- Lucia Minoli3,
- Paola Allavena4,
- Paola Cappello5,6,7,
- Francesco Novelli5,6,7,
- Aldo Scarpa8,
- Eugenio Morandi9,
- Anna Falanga10,
- Valter Torri2,
- Giulia Taraboletti1,‡,
- Dorina Belotti (dorina.belotti{at}marionegri.it)*,1,‡ and
- Raffaella Giavazzi (raffaella.giavazzi{at}marionegri.it)*,1,‡
- 1Laboratory of Biology and Treatment of Metastasis, Department of Oncology, IRCCS‐Istituto di Ricerche Farmacologiche Mario Negri, Bergamo and Milan, Italy
- 2Laboratory of Methodology for Clinical Research, Department of Oncology, IRCCS‐Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy
- 3Mouse and Animal Pathology Lab, Fondazione Filarete and Department of Veterinary Pathology, University of Milan, Milan, Italy
- 4Department of Immunology and Inflammation, IRCCS‐Humanitas Clinical and Research Center, Rozzano, Italy
- 5CERMS, AOU Città della Salute e della Scienza, Turin, Italy
- 6Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy
- 7Molecular Biotechnology Center, Turin, Italy
- 8Department of Pathology and Diagnostic, University and Hospital Trust of Verona, Verona, Italy
- 9Chirurgia IV, Presidio Ospedaliero di Rho, ASST Rhodense, Milano, Italy
- 10Department of Immunohematology and Transfusion Medicine, Thrombosis and Hemostasis Center, Hospital Papa Giovanni XXIII, Bergamo, Italy
- ↵*
Corresponding author. Tel: +39 035 42131; Fax: +39 035 319331; E‐mail: dorina.belotti{at}marionegri.it
Corresponding author. Tel: +39 02 39014732; Fax: +39 02 39014734; E‐mail: raffaella.giavazzi{at}marionegri.it
Seven stroma‐related circulating biomarkers that discriminate between healthy subjects and pancreatic ductal adenocarcinoma (PDAC) in two different cohorts of patients have been identified and suggested as a potential diagnosis tool to monitor treatment efficacy in patients.
Synopsis
Seven stroma‐related circulating biomarkers that discriminate between healthy subjects and pancreatic ductal adenocarcinoma (PDAC) in two different cohorts of patients have been identified and suggested as a potential diagnosis tool to monitor treatment efficacy in patients.
Panels of biomarkers that improve the performance of CA19.9 in distinguishing i) PDAC from healthy subjects and ii) PDAC from chronic pancreatitis have been developed. Multivariable models confirmed their predictive accuracy at early stages of disease.
The association of these biomarkers with the development of pre‐invasive disease in GEM models confirmed their potential to detect early stage lesions.
The correlation of biomarker levels with tumor burden and drug response in patient‐derived PDAC xenograft models indicate their value to monitor treatment response and efficacy.
EMBO Mol Med (2018) 10: e8741
- Received December 1, 2017.
- Revision received May 25, 2018.
- Accepted June 1, 2018.
- © 2018 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Amyloid blood biomarker detects Alzheimer's disease
- Andreas Nabers1,†,
- Laura Perna2,†,
- Julia Lange1,
- Ute Mons2,
- Jonas Schartner1,
- Jörn Güldenhaupt1,
- Kai‐Uwe Saum2,
- Shorena Janelidze3,
- Bernd Holleczek4,
- Dan Rujescu5,
- Oskar Hansson3,6,
- Klaus Gerwert (gerwert{at}bph.rub.de)*,1,‡ and
- Hermann Brenner2,7
- 1Department of Biophysics, Ruhr‐University Bochum, Bochum, Germany
- 2Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
- 3Department of Clinical Sciences, Lund University, Lund, Sweden
- 4Saarland Cancer Registry, Saarbrücken, Germany
- 5Department of Psychiatry, Psychotherapy and Psychosomatics, University of Halle, Halle, Germany
- 6Memory Clinic, Skåne University Hospital, Malmö, Sweden
- 7Network Aging Research (NAR), University of Heidelberg, Heidelberg, Germany
- ↵*Corresponding author. Tel: +49 234 32 24462; E‐mail: gerwert{at}bph.rub.de
↵† These authors contributed equally to this work
Determination of the amyloid‐β secondary structure distribution in blood plasma by an immuno‐IR‐sensor correlates with PET scanning and CSF markers in Alzheimer's disease (AD) patients, with potentials to be an accurate, simple, and minimally invasive biomarker for early AD detection.
Synopsis
Determination of the amyloid‐β secondary structure distribution in blood plasma by an immuno‐IR‐sensor correlates with PET scanning and CSF markers in Alzheimer's disease (AD) patients, with potentials to be an accurate, simple, and minimally invasive biomarker for early AD detection.
The amyloid‐β (Aβ) secondary structure distribution in blood plasma can be directly determined by the secondary structure sensitive amide I band.
Prodromal AD cases (BioFINDER study) showed significant correlations between the amide I frequency shift and PET scanning results or CSF biomarker values.
Early AD identification (Esther) yielded in 71% sensitivity, 91% specificity, and a LR+ of 7.9–8 years before clinical symptoms appeared, in agreement with the BioFINDER study.
The plasma biomarker may be used as a routine minimal‐invasive, low‐cost funnel to pre‐select individuals which should undergo lumbar puncture or PET scanning.
EMBO Mol Med (2018) 10: e8763
- Received December 7, 2017.
- Revision received March 2, 2018.
- Accepted March 6, 2018.
- © 2018 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- 18F‐AV‐1451 and CSF T‐tau and P‐tau as biomarkers in Alzheimer's disease
- Niklas Mattsson (niklas.mattsson{at}med.lu.se)*,1,2,3,
- Michael Schöll1,4,
- Olof Strandberg1,
- Ruben Smith1,3,
- Sebastian Palmqvist1,3,
- Philip S Insel1,5,6,
- Douglas Hägerström7,
- Tomas Ohlsson8,
- Henrik Zetterberg9,10,11,
- Jonas Jögi12,
- Kaj Blennow9,10 and
- Oskar Hansson (oskar.hansson{at}med.lu.se)*,1,2
- 1Clinical Memory Research Unit, Faculty of Medicine, Lund University, Lund, Sweden
- 2Memory Clinic, Skåne University Hospital, Lund, Sweden
- 3Department of Neurology, Skåne University Hospital, Lund, Sweden
- 4MedTech West and the Department of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg, Sweden
- 5Department of Veterans Affairs Medical Center, Center for Imaging of Neurodegenerative Diseases, San Francisco, CA, USA
- 6Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA
- 7Department of Clinical Neurophysiology, Skåne University Hospital, Lund, Sweden
- 8Department of Radiation physics, Skåne University Hospital, Lund, Sweden
- 9Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
- 10Department of Molecular Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
- 11Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK
- 12Department of Clinical Physiology and Nuclear Medicine, Skåne University Hospital, Lund, Sweden
- ↵*
Corresponding author. Tel: +46 (0)46 171000; E‐mail: niklas.mattsson{at}med.lu.se
Corresponding author. Tel: +46 (0)40 331000; E‐mail: oskar.hansson{at}med.lu.se
Tau pathology is a key feature of Alzheimer's disease (AD) but the relationship between cerebrospinal fluid tau, the tau PET tracer 18F‐AV‐1451 and other hallmarks of AD is unclear. This is now studied in a cohort of cognitively healthy controls and patients with prodromal and dementia stages of AD.
Synopsis
Tau pathology is a key feature of Alzheimer's disease (AD) but the relationship between cerebrospinal fluid tau, the tau PET tracer 18F‐AV‐1451 and other hallmarks of AD is unclear. This is now studied in a cohort of cognitively healthy controls and patients with prodromal and dementia stages of AD.
Cerebrospinal fluid total‐tau and phosphorylated‐tau levels are moderately correlated with 18F‐AV‐1451 tau PET retention.
Correlations between cerebrospinal fluid tau and 18F‐AV‐1451 tau PET are seen primarily in the dementia stage of Alzheimer's disease.
Cerebrospinal fluid tau levels are increased already in preclinical AD.
18F‐AV‐1451 tau PET is more strongly related to neurodegeneration and cognitive decline than cerebrospinal fluid tau levels are.
Cerebrospinal fluid tau levels may be useful primarily to identify the presence of Alzheimer's disease, while 18F‐AV‐1451 tau PET may be useful also to track the progression of the disease.
EMBO Mol Med (2017) 9: 1212–1223
- Received March 16, 2017.
- Revision received June 14, 2017.
- Accepted June 20, 2017.
- © 2017 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Specific biomarkers for C9orf72 FTD/ALS could expedite the journey towards effective therapies
A hexanucleotide repeat expansion in the C9orf72 gene is a common genetic cause of ALS and FTD. The repeats are translated into five different dipeptide repeat proteins (DPRs). In this issue, Lehmer et al (2017) demonstrate that one of these DPRs, poly(GP), can be measured in the CSF of individuals with C9orf72 mutations. In conjunction with the findings from another recent study (Gendron et al, 2017), these DPR biomarkers may prove to be extremely valuable in the quest for effective therapies for C9FTD/ALS.
See also: C Lehmer et al (July 2017) and TF Gendron et al (March 2017)
Isaacs and colleagues discuss two recent studies showing how a dipeptide repeat protein, poly(GP), can be measured in the CSF of individuals with C9orf72 mutations and used as a valuable biomarker in the quest for effective therapies for C9FTD/ALS.
- © 2017 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Poly‐GP in cerebrospinal fluid links C9orf72‐associated dipeptide repeat expression to the asymptomatic phase of ALS/FTD
- Carina Lehmer1,†,
- Patrick Oeckl2,†,
- Jochen H Weishaupt2,
- Alexander E Volk3,
- Janine Diehl‐Schmid4,
- Matthias L Schroeter5,6,
- Martin Lauer7,
- Johannes Kornhuber8,
- Johannes Levin1,9,
- Klaus Fassbender10,
- Bernhard Landwehrmeyer2,
- German Consortium for Frontotemporal Lobar Degeneration‡,
- Martin H Schludi1,
- Thomas Arzberger1,11,12,
- Elisabeth Kremmer13,
- Andrew Flatley14,
- Regina Feederle1,14,
- Petra Steinacker2,
- Patrick Weydt2,15,
- Albert C Ludolph2,
- Dieter Edbauer (dieter.edbauer{at}dzne.de)*,1,† and
- Markus Otto (markus.otto{at}uni-ulm.de)*,2,†
- 1German Center for Neurodegenerative Diseases (DZNE) and Munich Cluster for System Neurology (SyNergy), Munich, Germany
- 2Department of Neurology, Ulm University Hospital, Ulm, Germany
- 3Institute of Human Genetics, University Medical Centre Hamburg‐Eppendorf, Hamburg, Germany
- 4Department of Psychiatry and Psychotherapy, Technical University of Munich, München, Germany
- 5Clinic for Cognitive Neurology, University Clinic Leipzig, Leipzig, Germany
- 6Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
- 7Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Würzburg, Germany
- 8Department of Psychiatry and Psychotherapy, Friedrich‐Alexander‐University of Erlangen‐Nuremberg, Erlangen, Germany
- 9Department of Neurology, Ludwig‐Maximilians‐University Universität München, Munich, Germany
- 10Department of Neurology, Saarland University, Homburg, Germany
- 11Center for Neuropathology and Prion Research, Ludwig‐Maximilians‐University Munich, Munich, Germany
- 12Department of Psychiatry and Psychotherapy, Ludwig‐Maximilians‐University Munich, Munich, Germany
- 13Institute of Molecular Immunology, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Munich, Germany
- 14Monoclonal Antibody Core Facility and Research Group, Institute for Diabetes and Obesity, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Munich, Germany
- 15Department of Neurodegenerative Diseases and Gerontopsychiatry, Bonn University Hospital, Bonn, Germany
- ↵*
Corresponding author. Tel: +49 89 4400 46510; E‐mail: dieter.edbauer{at}dzne.de
Corresponding author. Tel: +49 731 500 63010; Fax: +49 731 500 63012; E‐mail: markus.otto{at}uni-ulm.de
↵† These authors contributed equally to this work
The C9orf72 hexanucleotide repeat expansion causing amyotrophic lateral sclerosis and frontotemporal dementia is translated into five dipeptide repeat (DPR) proteins, including poly‐GP. Analysis of poly‐GP levels in the CSF of patients and presymptomatic carriers support an early role of DPRs in pathogenesis.
Synopsis
The C9orf72 hexanucleotide repeat expansion causing amyotrophic lateral sclerosis and frontotemporal dementia is translated into five dipeptide repeat (DPR) proteins, including poly‐GP. Analysis of poly‐GP levels in the CSF of patients and presymptomatic carriers support an early role of DPRs in pathogenesis.
Monoclonal immunoassay detects poly‐GP in CSF of C9orf72 patients.
Poly‐GP levels in asymptomatic carriers and c9ALS/FTD patients are similar.
Neurofilaments but not poly‐GP levels correlate with clinical disease progression.
EMBO Mol Med (2017) 9: 859–868
- Received December 19, 2016.
- Revision received March 27, 2017.
- Accepted March 28, 2017.
- © 2017 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Non‐invasive lung cancer diagnosis by detection of GATA6 and NKX2‐1 isoforms in exhaled breath condensate
- Aditi Mehta1,‡,
- Julio Cordero1,‡,
- Stephanie Dobersch1,
- Addi J Romero‐Olmedo1,2,
- Rajkumar Savai3,4,†,
- Johannes Bodner5,
- Cho‐Ming Chao6,
- Ludger Fink7,†,
- Ernesto Guzmán‐Díaz8,
- Indrabahadur Singh1,
- Gergana Dobreva9,
- Ulf R Rapp3,†,
- Stefan Günther10,
- Olga N Ilinskaya11,
- Saverio Bellusci6,11,†,
- Reinhard H Dammann12,†,
- Thomas Braun10,†,
- Werner Seeger3,4,†,
- Stefan Gattenlöhner13,
- Achim Tresch14,15,
- Andreas Günther4,16,† and
- Guillermo Barreto (guillermo.barreto{at}mpi-bn.mpg.de)*,1,11,†
- 1LOEWE Research Group Lung Cancer Epigenetic, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
- 2Facultad de Ciencias Químicas, Universidad Autonoma “Benito Juarez” de Oaxaca, Oaxaca, Mexico
- 3Department of Lung Development and Remodeling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
- 4Pulmonary and Critical Care Medicine, Department of Internal Medicine, Justus Liebig University, Giessen, Germany
- 5Section Thoracic Surgery, Justus Liebig University, Giessen, Germany
- 6Chair for Lung Matrix Remodeling, Excellence Cluster Cardio Pulmonary System, Justus Liebig University, Giessen, Germany
- 7Institute of Pathology and Cytology, UEGP, Wetzlar, Germany
- 8Regional Hospital of High Specialties of Oaxaca (HRAEO), Oaxaca, Mexico
- 9Emmy Noether Research Group Origin of Cardiac Cell Lineages, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
- 10Department of Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
- 11Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, Kazan, Russian Federation
- 12Institute for Genetics, Justus Liebig University, Giessen, Germany
- 13Institute for Pathology, Justus Liebig University, Giessen, Germany
- 14Max Planck Institute for Plant Breeding Research, Cologne, Germany
- 15University of Cologne, Cologne, Germany
- 16Agaplesion Lung Clinic Waldhof Elgershausen, Greifenstein, Germany
- ↵*Corresponding author. Tel: +49 6032 705259; E‐mail: guillermo.barreto{at}mpi-bn.mpg.de
↵‡ These authors contributed equally to this work
Early diagnosis is critical to improving lung cancer (LC) patient prognosis. An accurate, non‐invasive LC diagnostic test was developed based on expression analysis of embryonic vs. adult GATA6 and NKX2‐1 gene isoforms in exhaled breath condensates.
Synopsis
Early diagnosis is critical to improving lung cancer (LC) patient prognosis. An accurate, non‐invasive LC diagnostic test was developed based on expression analysis of embryonic vs. adult GATA6 and NKX2‐1 gene isoforms in exhaled breath condensates.
Embryonic and adult isoforms of GATA6 and NKX2‐1 are differentially expressed during mouse lung development and in lung cancer.
RNA purified from exhaled breath condensates (EBC) can be used for qRT–PCR‐based expression analysis, despite the relatively high fragmentation of the isolated RNA.
Embryonic and adult isoforms of GATA6 and NKX2‐1 detected in EBC can be combined into the LC score for LC diagnosis at stages I and II.
EMBO Mol Med (2016) 8: 1380–1389
- Received March 8, 2016.
- Revision received September 23, 2016.
- Accepted September 28, 2016.
- © 2016 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- New CSF biomarkers on the block
A growing number of cerebrospinal fluid biomarkers are now available to capture different aspects of Alzheimer's disease. People are increasingly aware that these biomarkers represent a real‐time reflection of pathological mechanisms that are ongoing in the brain. These novel markers can be added to the panel of existing ones like amyloid beta, total Tau and phosphoTau that are currently used for sensitive diagnosis of Alzheimer's disease, either alone or in combination.
See also: N Mattsson et al (October 2016)
A growing number of cerebrospinal fluid biomarkers are becoming available for Alzheimer's disease. In this issue of EMBO Molecular Medicine, Mattsson et al propose a new combination of these to capture different aspects of Alzheimer's disease in patients.
- © 2016 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Cerebrospinal fluid tau, neurogranin, and neurofilament light in Alzheimer's disease
- Niklas Mattsson (niklas.mattsson{at}med.lu.se)*,1,2,
- Philip S Insel1,3,
- Sebastian Palmqvist1,2,
- Erik Portelius4,
- Henrik Zetterberg4,5,
- Michael Weiner3,
- Kaj Blennow4,
- Oskar Hansson (oskar.hansson{at}med.lu.se)*,1,2,
- the Alzheimer's Disease Neuroimaging Initiative†
- 1Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden
- 2Department of Neurology, Skåne University Hospital, Lund, Sweden
- 3Department of Radiology, University of California San Francisco, San Francisco, CA, USA
- 4Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden
- 5Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK
- ↵*
Corresponding author. Tel: +46 72 575 9329; E‐mail: niklas.mattsson{at}med.lu.se
Corresponding author. Tel: +46 40 33 50 36; E‐mail: oskar.hansson{at}med.lu.se
Different cerebrospinal fluid (CSF) biomarkers have been proposed to measure neurodegeneration in AD. These biomarkers include tau (total tau, T‐tau), neurofilament light (NFL) and neurogranin (Ng), but it is unknown to what degree they provide overlapping or complementing information in AD.
Synopsis
Different cerebrospinal fluid (CSF) biomarkers have been proposed to measure neurodegeneration in AD. These biomarkers include tau (total tau, T‐tau), neurofilament light (NFL) and neurogranin (Ng), but it is unknown to what degree they provide overlapping or complementing information in AD.
Combinations of CSF T‐tau, Ng and NFL may improve the diagnostic accuracy for AD.
CSF T‐tau, Ng and NFL have significant and different associations with distinct hallmarks of neurodegeneration, including cognitive decline and structural and functional brain changes.
CSF T‐tau and Ng are closely associated with β‐amyloid‐dependent degeneration, while NFL is associated with neurodegeneration independently of β‐amyloid pathology.
EMBO Mol Med (2016) 8: 1184–1196
- Received April 25, 2016.
- Revision received June 22, 2016.
- Accepted July 8, 2016.
- © 2016 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- CSF sTREM2: marking the tipping point between preclinical AD and dementia?
Biomarkers for Alzheimer's disease (AD) have improved our understanding of the temporal sequence of biological events that lead to AD dementia (Jack et al, 2013). AD is characterized neuropathologically by amyloid plaques comprised of the amyloid‐β peptide and neurofibrillary tangles comprised of tau. Brain amyloid deposition, as evidenced by a decline in amyloid‐β peptide 42 (Aβ42) in the cerebrospinal fluid (CSF) or by binding of amyloid PET ligands, is thought to be a key initiating event in AD and begins many years prior to the onset of dementia. A rise in CSF tau and phosphorylated tau in the setting of Aβ deposition appears to reflect neurodegeneration and also begins years prior to the onset of dementia but after Aβ deposition has begun to accumulate. Individuals with “preclinical AD,” that is, normal cognition but abnormal AD biomarkers, have a much higher risk for developing AD dementia but may remain cognitively normal for years (Vos et al, 2013). While deposition of amyloid and formation of tau tangles are necessary for AD to occur, it is likely that additional events involving inflammation or other processes contribute to crossing the tipping point from preclinical AD to AD dementia. Current efforts are aimed at defining the biomarker(s) that best predict the transition from cognitive normality to abnormality. A biomarker that is closely associated with the onset of cognitive decline could help us to understand the biological events that connect amyloid deposition and tangle formation to cognitive decline and could have significant practical value in AD diagnosis and clinical trial design.
See also: M Suárez-Calvet et al (May 2016)
Schindler and Holtzman highlight the work of Suarez‐Calvet et al in this issue as they report that cerebrospinal fluid sTREM2 levels are associated with the onset of cognitive decline in Alzheimer's disease, a significant finding for AD diagnostics and drug trials.
- © 2016 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
ICI - sTREM2 cerebrospinal fluid levels are a potential biomarker for microglia activity in early‐stage Alzheimer's disease and associate with neuronal injury markers
- Marc Suárez‐Calvet1,2,
- Gernot Kleinberger1,3,
- Miguel Ángel Araque Caballero4,
- Matthias Brendel5,
- Axel Rominger3,5,
- Daniel Alcolea6,7,
- Juan Fortea6,7,
- Alberto Lleó6,7,
- Rafael Blesa6,7,
- Juan Domingo Gispert8,9,
- Raquel Sánchez‐Valle10,11,
- Anna Antonell10,11,
- Lorena Rami10,11,
- José L Molinuevo8,9,10,11,
- Frederic Brosseron12,
- Andreas Traschütz13,
- Michael T Heneka12,13,
- Hanne Struyfs14,15,
- Sebastiaan Engelborghs14,15,
- Kristel Sleegers16,17,
- Christine Van Broeckhoven16,17,
- Henrik Zetterberg18,19,
- Bengt Nellgård20,
- Kaj Blennow18,
- Alexander Crispin21,
- Michael Ewers*,4,† and
- Christian Haass*,1,2,3,†
- 1BioMedical Center (BMC), Biochemistry, Ludwig‐Maximilians‐University Munich, Munich, Germany
- 2German Center for Neurodegenerative Diseases (DZNE) Munich, Munich, Germany
- 3Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
- 4Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig‐Maximilians‐University Munich, Munich, Germany
- 5Department of Nuclear Medicine, Klinikum der Universität München, Ludwig‐Maximilians‐University Munich, Munich, Germany
- 6Department of Neurology, Institut d'Investigacions Biomèdiques Hospital de la Santa Creu i Sant Pau Universitat Autònoma de Barcelona, Barcelona, Spain
- 7Center for Networked Biomedical Research for Neurodegenerative Diseases, CIBERNED, Madrid, Spain
- 8Clinical and Neuroimaging Departments, Barcelona Beta Brain Research Center Pasqual Maragall Foundation, Barcelona, Spain
- 9Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER‐BBN), Barcelona, Spain
- 10Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, ICN Hospital Clinic i Universitari, Barcelona, Spain
- 11Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- 12German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
- 13Neurology Department, Universitätsklinikum Bonn, Bonn, Germany
- 14Reference Center for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behavior, Institute Born‐Bunge University of Antwerp, Antwerp, Belgium
- 15Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium
- 16Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
- 17Laboratory of Neurogenetics, Institute Born‐Bunge University of Antwerp, Antwerp, Belgium
- 18Clinical Neurochemistry Lab, Institute of Neuroscience and Physiology The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
- 19Reta Lila Weston Laboratories and Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK
- 20Department of Anaesthesiology and Intensive Care, Institute of Clinical Sciences Sahlgrenska Academy Gothenburg University, Gothenburg, Sweden
- 21Institute of Medical Informatics, Biometry, and Epidemiology, Munich, Germany
- ↵*
Corresponding author. Tel: +49 89 4400 46221; Fax: +49 89 4400 46113; E‐mail: michael.ewers{at}med.uni-muenchen.de
Corresponding author. Tel: +49 89 4400 46549; Fax: +49 89 4400 46546; E‐mail: christian.haass{at}mail03.med.uni-muenchen.de
↵† These authors contributed equally to this study
TREM2 is an innate immune receptor selectively expressed by microglia in the brain. Measuring its soluble variant in the CSF (sTREM2) may be a candidate as a marker of microglial activity. This study aimed to investigate how CSF sTREM2 levels change during the course of Alzheimer's disease (AD).
Synopsis
TREM2 is an innate immune receptor selectively expressed by microglia in the brain. Measuring its soluble variant in the CSF (sTREM2) may be a candidate as a marker of microglial activity. This study aimed to investigate how CSF sTREM2 levels change during the course of Alzheimer's disease (AD).
CSF sTREM2 levels are increased in the mild cognitive impairment (MCI) stage of AD compared to controls (P = 0.002), and to the preclinical (trend level, P = 0.062), and dementia stage of AD (P = 0.013).
CSF sTREM2 levels are increased in individuals with suspected non‐AD pathology (SNAP) compared to controls (P = 0.0004).
CSF sTREM2 levels increase with aging.
Increased CSF sTREM2 levels are associated with higher levels of T‐tau and P‐tau181P, markers of neuronal cell injury, and neurofibrillary tangles.
EMBO Mol Med (2016) 8: 466–476
- Received December 3, 2015.
- Revision received January 27, 2016.
- Accepted January 28, 2016.
- © 2016 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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