Inflammatory biomarkers in Alzheimer's disease plasma.
Morgan ARSystems Immunity Research Institute and UK Dementia Research Institute Cardiff, School of Medicine, Cardiff University, Cardiff, UK.
Touchard SSystems Immunity Research Institute and UK Dementia Research Institute Cardiff, School of Medicine, Cardiff University, Cardiff, UK.
Leckey CSystems Immunity Research Institute and UK Dementia Research Institute Cardiff, School of Medicine, Cardiff University, Cardiff, UK.
O'Hagan CSystems Immunity Research Institute and UK Dementia Research Institute Cardiff, School of Medicine, Cardiff University, Cardiff, UK.
Nevado-Holgado AJDepartment of Psychiatry, University of Oxford, Oxford, UK.
Barkhof FMax Planck Institute for Molecular Genetics, Berlin, Germany.
Bertram LAix-Marseille University, APHM, Institute Neurosci System, Pharmacology, Marseille, France.
Blin OAlzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands.
Bos ILübeck Interdisciplinary Platform for Genome Analytics, University of Lübeck, Lübeck, Germany.
Dobricic VDepartment of Neurology, Hospital Network Antwerp (ZNA), Antwerp, Belgium; Reference Center for Biological Markers of Dementia, Institute Born-Bunge, Antwerp, Belgium.
Engelborghs SUniversity of Geneva, Geneva, Switzerland; IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
Frisoni GDepartment of Geriatric Psychiatry, Zentralinstitut für Seelische Gesundheit, University of Heidelberg, Mannheim, Germany.
Frölich LDepartment of Neurosciences, Laboratory for Cognitive Neurology, KU Leuven, Leuven, Belgium.
Gabel SDivision of Clinical Geriatrics, Department of Neurobiology, Caring Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
Johannsen PUniversity of Gothenburg, Institute of Neuroscience and Physiology, Gothenburg, Sweden.
Kettunen PDepartment of Old Age Psychiatry & Psychotic Disorders, Medical University of Lodz, Lodz, Poland.
Kłoszewska IUCL Institutes of Neurology and Healthcare Engineering, University College London, London, UK; School of Public Health, Imperial College London, London, UK.
Legido-Quigley CDepartment of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Lleó ACITA-Alzheimer Foundation, San Sebastian, Spain.
Martinez-Lage PDepartment of Medicine, Institute of Gerontology and Geriatrics, University of Perugia, Perugia, Italy.
Mecocci PDepartment of Neurosciences, Laboratory for Cognitive Neurology, KU Leuven, Leuven, Belgium.
Meersmans KBarcelona Beta Brain Research Center, Unversitat Pompeu Fabra, Barcelona, Spain.
Molinuevo JLDepartment of Psychiatry, Old Age Psychiatry, Lausanne University Hospital, Lausanne, Switzerland.
Peyratout GHopitaux Universitaires Geneve and Universite de Geneve, Geneva, Switzerland.
Teunissen C1st Department of Neurology, AHEPA University Hospital, Makedonia, Thessaloniki, Greece.
Tsolaki MDepartment of Clinical Chemistry, Neurochemistry lab, Amsterdam University Medical Centers, Amsterdam, the Netherlands.
Vandenberghe RDepartment of Psychiatry & Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands.
Visser PJAlzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands.
Vos SNVS-Department, Section of Clinical Geriatrics, Karolinska Institutet, Huddinge, Sweden.
Wahlund LOSection for Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg Sahlgrenska Academy, Gothenburg, Sweden.
Wallin ADepartment of Psychiatry, University of Oxford, Oxford, UK.
Westwood SClinical Neurochemistry Lab, Institute of Neuroscience and Physiology, Sahlgrenska University Hospital, Mölndal, Sweden; Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, University of Gothenburg, Mölndal, Sweden; Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK; UK Dementia Research Institute, London, UK.
Zetterberg HDepartment of Psychiatry, University of Oxford, Oxford, UK.
Lovestone SSystems Immunity Research Institute and UK Dementia Research Institute Cardiff, School of Medicine, Cardiff University, Cardiff, UK. Electronic address: morganbp@cardiff.ac.uk.
English
INTRODUCTION Plasma biomarkers for Alzheimer's disease (AD) diagnosis/stratification are a "Holy Grail" of AD research and intensively sought; however, there are no well-established plasma markers.
METHODS A hypothesis-led plasma biomarker search was conducted in the context of international multicenter studies. The discovery phase measured 53 inflammatory proteins in elderly control (CTL; 259), mild cognitive impairment (MCI; 199), and AD (262) subjects from AddNeuroMed.
RESULTS Ten analytes showed significant intergroup differences. Logistic regression identified five (FB, FH, sCR1, MCP-1, eotaxin-1) that, age/APOε4 adjusted, optimally differentiated AD and CTL (AUC: 0.79), and three (sCR1, MCP-1, eotaxin-1) that optimally differentiated AD and MCI (AUC: 0.74). These models replicated in an independent cohort (EMIF; AUC 0.81 and 0.67). Two analytes (FB, FH) plus age predicted MCI progression to AD (AUC: 0.71).
DISCUSSION Plasma markers of inflammation and complement dysregulation support diagnosis and outcome prediction in AD and MCI. Further replication is needed before clinical translation.