Cerebrospinal fluid proteomic profiling of individuals with mild cognitive impairment and suspected non-Alzheimer's disease pathophysiologyAlzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands.
Lübeck Interdisciplinary Platform for Genome Analytics, University of Lübeck, Lübeck, Germany.
Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; Department of Radiology and Nuclear Medicine, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands .
Department of Psychiatry and Neuropsychology, Alzheimer Centrum Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands.
Department of Psychiatry and Neuropsychology, Alzheimer Centrum Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands.
Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands.
Neurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam University Medical Centers (AUMC), Amsterdam Neuroscience, the Netherlands.
Neurology Service, University Hospitals Leuven, Leuven, Belgium; Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium.
Neurology Service, University Hospitals Leuven, Leuven, Belgium; Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium.
Neurology Service, University Hospitals Leuven, Leuven, Belgium; Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium.
Old Age Psychiatry, University Hospital Lausanne, Lausanne, Switzerland; Department of Geriatric Psychiatry, Psychiatry University Hospital Zürich, Zürich, Switzerland.
Old Age Psychiatry, University Hospital Lausanne, Lausanne, Switzerland.
Fundación CITA-Alzhéimer Fundazioa, San Sebastian, Spain.
Fundación CITA-Alzhéimer Fundazioa, San Sebastian, Spain.
1st Department of Neurology, AHEPA University Hospital, Medical School, Faculty of Health Sciences, Aristotle University of Thessaloniki, Makedonia, Thessaloniki, Greece.
University of Oxford, Oxford, United Kingdom (currently at Johnson and Johnson Medical Ltd.), London, UK.
Institute Born-Bunge, Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Belgium; UCB Biopharma SPRL, Brain-l'Alleud, Belgium.
Department of Radiology and Nuclear Medicine, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands; Institutes of Neurology & Healthcare Engineering, UCL London, London, UK .
Lübeck Interdisciplinary Platform for Genome Analytics, University of Lübeck, Lübeck, Germany; Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway .
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK; UK Dementia Research Institute at UCL, London, UK.
Department of Psychiatry and Neuropsychology, Alzheimer Centrum Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands; Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; Department of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Karolinska Institutet, Stockholm, Sweden.
Department of Psychiatry and Neuropsychology, Alzheimer Centrum Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands.
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2023 (English)In: Alzheimer's & Dementia: Journal of the Alzheimer's Association, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 19, no 3, p. 807-820Article in journal (Refereed) Published
Abstract [en]
BACKGROUND: Suspected non-Alzheimer's disease pathophysiology (SNAP) is a biomarker concept that encompasses individuals with neuronal injury but without amyloidosis. We aim to investigate the pathophysiology of SNAP, defined as abnormal tau without amyloidosis, in individuals with mild cognitive impairment (MCI) by cerebrospinal fluid (CSF) proteomics.
METHODS: Individuals were classified based on CSF amyloid beta (Aβ)1-42 (A) and phosphorylated tau (T), as cognitively normal A-T- (CN), MCI A-T+ (MCI-SNAP), and MCI A+T+ (MCI-AD). Proteomics analyses, Gene Ontology (GO), brain cell expression, and gene expression analyses in brain regions of interest were performed.
RESULTS: A total of 96 proteins were decreased in MCI-SNAP compared to CN and MCI-AD. These proteins were enriched for extracellular matrix (ECM), hemostasis, immune system, protein processing/degradation, lipids, and synapse. Fifty-one percent were enriched for expression in the choroid plexus.
CONCLUSION: The pathophysiology of MCI-SNAP (A-T+) is distinct from that of MCI-AD. Our findings highlight the need for a different treatment in MCI-SNAP compared to MCI-AD.
Place, publisher, year, edition, pages
John Wiley & Sons, 2023. Vol. 19, no 3, p. 807-820
Keywords [en]
Alzheimer's disease, biomarkers, cerebrospinal fluid, mild cognitive impairment, pathophysiology, proteomics, suspected non-Alzheimer's disease pathophysiology, tau
National Category
Neurology
Identifiers
URN: urn:nbn:se:oru:diva-99623DOI: 10.1002/alz.12713ISI: 000810391000001PubMedID: 35698882Scopus ID: 2-s2.0-85131726329OAI: oai:DiVA.org:oru-99623DiVA, id: diva2:1670716
Funder
The Swedish Brain Foundation, FO2018-0315Stiftelsen Gamla TjänarinnorThe Kamprad Family Foundation, 20210034 AFA 200386
Note
Funding agencies:
Memorabel program of ZonMw (Netherlands Organization for Health Research and Development) 733050502
Johnson & Johnson USA Janssen Biotech Inc
EMIF-AD EMIF from the European Union 115372
European Commission Joint Research Centre QLRT-2001- 2455 37670
Department of Health of the Basque Government 17.0.1.08.12.0000.2.454.01.41142.001.H
Provincial Government of Gipuzkoa 124/16
Kutxa Fundazioa
Instituto de Salud Carlos III PI15/00919
Swiss National Science Foundation (SNSF) SNF 320030_141179
Stichting Alzheimer Onderzoek
Stohne's Foundation (Stohnes Stiftelse)
Sarfond 31S Research Fund Region Örebro län Sweden
NIHR biomedical reserach center at UCLH
2022-06-162022-06-162023-05-11Bibliographically approved