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  • Tijms, B. M.Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam UMC, Amsterdam, The Netherlands (författare)

CSF Proteomic Alzheimer's Disease-Predictive Subtypes in Cognitively Intact Amyloid Negative Individuals

  • Artikel/kapitelEngelska2021

Förlag, utgivningsår, omfång ...

  • 2021-08-02
  • MDPI AG,2021

Nummerbeteckningar

  • LIBRIS-ID:oai:gup.ub.gu.se/310184
  • https://gup.ub.gu.se/publication/310184URI
  • https://doi.org/10.3390/proteomes9030036DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-93951URI

Kompletterande språkuppgifter

  • Språk:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Funding agencies:ZonMW Memorabel Grant programme 733050824Innovative Medicines Initiative Joint undertaking under EMIF grant 115372European Research Council (ERC) 681712Stichting Alzheimer NederlandStichting VUmc fondsUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Neurological Disorders & Stroke (NINDS) U01 AG024904  DOD ADNI (Department of Defense) W81XWH-12-20012NIH National Institute on Aging (NIA) NIH National Institute of Biomedical Imaging & Bioengineering (NIBIB) AbbVie Alzheimer's Association Alzheimer's Drug Discovery Foundation Araclon Biotech BioClinica, Inc. Biogen Bristol-Myers Squibb CereSpir, Inc. Cogstate Eisai Co Ltd Elan Pharmaceuticals, Inc. Eli Lilly EuroImmun F. Hoffmann-La Roche Ltd. and its affiliated company Genentech, Inc. Fujirebio General ElectricGE Healthcare  IXICO Ltd. Janssen Alzheimer Immunotherapy Research & Development, LLC. Johnson & Johnson USA Lumosity Lundbeck Corporation Merck & Company Meso Scale Diagnostics, LLC. NeuroRx Research Neurotrack Technologies Novartis Piramal Imaging Servier Takeda Pharmaceutical Company Ltd Transition Therapeutics Canadian Institutes of Health Research (CIHR)
  • We recently discovered three distinct pathophysiological subtypes in Alzheimer's disease (AD) using cerebrospinal fluid (CSF) proteomics: one with neuronal hyperplasticity, a second with innate immune system activation, and a third subtype with blood-brain barrier dysfunction. It remains unclear whether AD proteomic subtype profiles are a consequence of amyloid aggregation, or might exist upstream from aggregated amyloid. We studied this question in 127 older individuals with intact cognition and normal AD biomarkers in two independent cohorts (EMIF-AD MBD and ADNI). We clustered 705 proteins measured in CSF that were previously related to AD. We identified in these cognitively intact individuals without AD pathology three subtypes: two subtypes were seen in both cohorts (n = 49 with neuronal hyperplasticity and n = 44 with blood-brain barrier dysfunction), and one only in ADNI (n = 12 with innate immune activation). The proteins specific for these subtypes strongly overlapped with AD subtype protein profiles (overlap coefficients 92%-71%). Longitudinal p(181)-tau and amyloid beta 1-42 (A beta 42) CSF analysis showed that in the hyperplasticity subtype p(181)-tau increased (beta = 2.6 pg/mL per year, p = 0.01) and A beta 42 decreased over time (beta = -4.4 pg/mL per year, p = 0.03), in the innate immune activation subtype p(181)-tau increased (beta = 3.1 pg/mL per year, p = 0.01) while in the blood-brain barrier dysfunction subtype A beta 42 decreased (beta = -3.7 pg/mL per year, p = 0.009). These findings suggest that AD proteomic subtypes might already manifest in cognitively normal individuals and may predispose for AD before amyloid has reached abnormal levels.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Gobom, JohanGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,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(Swepub:gu)xgobjo (författare)
  • Teunissen, C.Neurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam University Medical Centers (AUMC), Amsterdam Neuroscience, Amsterdam, The Netherlands (författare)
  • Dobricic, V.Lübeck Interdisciplinary Platform for Genome Analytics, University of Lübeck, Lübeck, Germany (författare)
  • Tsolaki, M.1st Department of Neurology, AHEPA University Hospital, Makedonia, Thessaloniki, Greece (författare)
  • Verhey, F.Alzheimer Center Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands (författare)
  • Popp, J.Old Age Psychiatry, University Hospital Lausanne, Lausanne, Switzerland; Department of Geriatric Psychiatry, University Hospital of Psychiatry and University of Zürich, Zürich, Switzerland (författare)
  • Martinez-Lage, P.Fundación CITA-Alzhéimer Fundazioa, San Sebastian, Spain (författare)
  • Vandenberghe, R.Neurology Service, University Hospitals Leuven, Leuven, Belgium; Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium (författare)
  • Lleo, A.IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain (författare)
  • Molinuevo, J. L.Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain; Alzheimer's Disease Unit and Other Cognitive Disorders Unit, Hospital Clinic de Barcelona, Barcelona, Spain (författare)
  • Engelborghs, S.Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerpen, Belgium; Department of Neurology, Universitair Ziekenhuis Brussel and Center for Neurosciences, Vrije Universiteit Brussel, Brussels, Belgium (författare)
  • Freund-Levi, Yvonne,1956-Örebro universitet,Institutionen för medicinska vetenskaper,Center for Alzheimer Research, Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden(Swepub:oru)yfi (författare)
  • Froelich, L.Department of Geriatric Psychiatry, Zentralinstitut für Seelische Gesundheit, University of Heidelberg, Mannheim, Germany (författare)
  • Bertram, L.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 (författare)
  • Lovestone, S.University of Oxford, Oxford, UK (författare)
  • Streffer, J.Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerpen, Belgium; AC Immune SA, Lausanne, Switzerland (författare)
  • Vos, S.Alzheimer Center Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands (författare)
  • Blennow, Kaj,1958Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,Alzheimer Center Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands,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(Swepub:gu)xbleka (författare)
  • Scheltens, P.Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam, The Netherlands (författare)
  • Zetterberg, H.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 (författare)
  • Visser, P. J.Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam, The Netherlands; Alzheimer Center Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands; Center for Alzheimer Research, Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden (författare)
  • Adni,, Adni, (författare)
  • Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam UMC, Amsterdam, The NetherlandsInstitutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Proteomes: MDPI AG9:32227-7382

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  • Proteomes (Sök värdpublikationen i LIBRIS)

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