Inflammatory biomarkers in Alzheimer's disease plasma |
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| Institution: | 1. Systems Immunity Research Institute and UK Dementia Research Institute Cardiff, School of Medicine, Cardiff University, Cardiff, UK;2. Department of Psychiatry, University of Oxford, Oxford, UK;3. Department of Radiology and Nuclear Medicine, VU University Medical, Amsterdam, the Netherlands;4. UCL Institutes of Neurology and Healthcare Engineering, University College London, London, UK;5. Max Planck Institute for Molecular Genetics, Berlin, Germany;6. Aix-Marseille University, APHM, Institute Neurosci System, Pharmacology, Marseille, France;7. Alzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands;8. Lübeck Interdisciplinary Platform for Genome Analytics, University of Lübeck, Lübeck, Germany;9. Department of Neurology, Hospital Network Antwerp (ZNA), Antwerp, Belgium;10. Reference Center for Biological Markers of Dementia, Institute Born-Bunge, Antwerp, Belgium;11. University of Geneva, Geneva, Switzerland;12. IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy;13. Department of Geriatric Psychiatry, Zentralinstitut für Seelische Gesundheit, University of Heidelberg, Mannheim, Germany;14. Department of Neurosciences, Laboratory for Cognitive Neurology, KU Leuven, Leuven, Belgium;15. Division of Clinical Geriatrics, Department of Neurobiology, Caring Sciences and Society, Karolinska Institutet, Stockholm, Sweden;p. University of Gothenburg, Institute of Neuroscience and Physiology, Gothenburg, Sweden;q. Department of Old Age Psychiatry & Psychotic Disorders, Medical University of Lodz, Lodz, Poland;r. School of Public Health, Imperial College London, London, UK;s. Department of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain;t. CITA-Alzheimer Foundation, San Sebastian, Spain;u. Department of Medicine, Institute of Gerontology and Geriatrics, University of Perugia, Perugia, Italy;v. Barcelona Beta Brain Research Center, Unversitat Pompeu Fabra, Barcelona, Spain;w. Department of Psychiatry, Old Age Psychiatry, Lausanne University Hospital, Lausanne, Switzerland;x. Hopitaux Universitaires Geneve and Universite de Geneve, Geneva, Switzerland;y. Neurosciences Therapeutic Area, GlaxoSmithKline R&D, Stevenage, UK;z. Memory Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain;11. Alzheimer Center, Amsterdam University Medical Centers, Vrije Universiteit, Amsterdam, the Netherlands;22. Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, Belgium;33. Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland;44. Center for Research and Advanced Therapies. CITA-Alzheimer Foundation, San Sebastian, Spain;55. University Hospital Leuven, Leuven, Belgium;66. 1st Department of Neurology, AHEPA University Hospital, Makedonia, Thessaloniki, Greece;77. Department of Clinical Chemistry, Neurochemistry lab, Amsterdam University Medical Centers, Amsterdam, the Netherlands;88. Department of Psychiatry & Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands;99. NVS-Department, Section of Clinical Geriatrics, Karolinska Institutet, Huddinge, Sweden;1010. Section for Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg Sahlgrenska Academy, Gothenburg, Sweden;1111. Clinical Neurochemistry Lab, Institute of Neuroscience and Physiology, Sahlgrenska University Hospital, Mölndal, Sweden;1212. Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, University of Gothenburg, Mölndal, Sweden;1313. Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK;1414. UK Dementia Research Institute, London, UK |
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| Abstract: | IntroductionPlasma 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.MethodsA 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.ResultsTen 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).DiscussionPlasma markers of inflammation and complement dysregulation support diagnosis and outcome prediction in AD and MCI. Further replication is needed before clinical translation. |
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| Keywords: | Alzheimer's disease Biomarker Plasma Inflammation Complement |
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