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| Fältnamn | Indikatorer | Metadata |
|---|---|---|
| 000 | 13563naa a2200937 4500 | |
| 001 | oai:gup.ub.gu.se/315298 | |
| 003 | SwePub | |
| 008 | 240528s2022 | |||||||||||000 ||eng| | |
| 009 | oai:DiVA.org:oru-98330 | |
| 009 | oai:prod.swepub.kib.ki.se:149137006 | |
| 024 | 7 | a https://gup.ub.gu.se/publication/3152982 URI |
| 024 | 7 | a https://doi.org/10.1186/s13024-022-00521-32 DOI |
| 024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-983302 URI |
| 024 | 7 | a http://kipublications.ki.se/Default.aspx?queryparsed=id:1491370062 URI |
| 040 | a (SwePub)gud (SwePub)orud (SwePub)ki | |
| 041 | a eng | |
| 042 | 9 SwePub | |
| 072 | 7 | a ref2 swepub-contenttype |
| 072 | 7 | a art2 swepub-publicationtype |
| 100 | 1 | a Visser, P. J.u Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands; Alzheimer Center Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands; Department of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Karolinska Institutet, Stockholm, Sweden,Old Age Psychiatry, University Hospital Lausanne, Lausanne, Switzerland; Department of Geriatric Psychiatry, University Hospital of Psychiatry and University of Zürich, Zürich, Switzerland4 aut |
| 245 | 1 0 | a Cerebrospinal fluid tau levels are associated with abnormal neuronal plasticity markers in Alzheimer's disease |
| 264 | c 2022-03-28 | |
| 264 | 1 | b Springer Science and Business Media LLC,c 2022 |
| 500 | a Funding agencies:ZonMW Memorabel grant programme 73305056 733050512 733050824Swedish State Support for Clinical Research ALFGBG-720931 Innovative Medicines Initiative Joint Undertaking under EMIF grant 115372Stichting Alzheimer Onderzoek 11020 15005 13007Vlaamse Impulsfinanciering voor Netwerken voor Dementie-onderzoek (IWT) 135043Swiss National Science Foundation (SNSF) 320030_141179United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Neurological Disorders & Stroke (NINDS) U01 AG024904NIH National Institute on Aging (NIA)NIH National Institute of Biomedical Imaging & Bioengineering (NIBIB)DOD ADNI (Department of Defense) W81XWH-12-2-0012AbbVieAlzheimer's AssociationAlzheimer's Drug Discovery FoundationAraclon BiotechBioClinica, Inc.BiogenBristol-Myers SquibbCereSpir, Inc.CogState LimitedEisai Co LtdElan Pharmaceuticals, Inc.Eli LillyEuroImmunHoffmann-La RocheRoche Holding GenentechFujirebioGeneral Electric GE HealthcareIXICO Ltd.Janssen Alzheimer Immunotherapy Research & Development, LLC.Johnson & Johnson USALumosityLundbeck CorporationMerck & CompanyMeso Scale Diagnostics, LLC.NeuroRx ResearchNeurotrack TechnologiesNovartisPiramal ImagingServierTakeda Pharmaceutical Company LtdTransition TherapeuticsCanadian Institutes of Health Research (CIHR) Correction: Cerebrospinal fluid tau levels are associated with abnormal neuronal plasticity markers in Alzheimer’s disease. Visser, P.J., Reus, L.M., Gobom, J. et al. Mol Neurodegeneration 17, 37 (2022). https://doi.org/10.1186/s13024-022-00540-0 | |
| 520 | a Background Increased total tau (t-tau) in cerebrospinal fluid (CSF) is a key characteristic of Alzheimer's disease (AD) and is considered to result from neurodegeneration. T-tau levels, however, can be increased in very early disease stages, when neurodegeneration is limited, and can be normal in advanced disease stages. This suggests that t-tau levels may be driven by other mechanisms as well. Because tau pathophysiology is emerging as treatment target for AD, we aimed to clarify molecular processes associated with CSF t-tau levels. Methods We performed a proteomic, genomic, and imaging study in 1380 individuals with AD, in the preclinical, prodromal, and mild dementia stage, and 380 controls from the Alzheimer's Disease Neuroimaging Initiative and EMIF-AD Multimodality Biomarker Discovery study. Results We found that, relative to controls, AD individuals with increased t-tau had increased CSF concentrations of over 400 proteins enriched for neuronal plasticity processes. In contrast, AD individuals with normal t-tau had decreased levels of these plasticity proteins and showed increased concentrations of proteins indicative of blood-brain barrier and blood-CSF barrier dysfunction, relative to controls. The distinct proteomic profiles were already present in the preclinical AD stage and persisted in prodromal and dementia stages implying that they reflect disease traits rather than disease states. Dysregulated plasticity proteins were associated with SUZ12 and REST signaling, suggesting aberrant gene repression. GWAS analyses contrasting AD individuals with and without increased t-tau highlighted several genes involved in the regulation of gene expression. Targeted analyses of SNP rs9877502 in GMNC, associated with t-tau levels previously, correlated in individuals with AD with CSF concentrations of 591 plasticity associated proteins. The number of APOE-e4 alleles, however, was not associated with the concentration of plasticity related proteins. Conclusions CSF t-tau levels in AD are associated with altered levels of proteins involved in neuronal plasticity and blood-brain and blood-CSF barrier dysfunction. Future trials may need to stratify on CSF t-tau status, as AD individuals with increased t-tau and normal t-tau are likely to respond differently to treatment, given their opposite CSF proteomic profiles. | |
| 650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Neurovetenskaper0 (SwePub)301052 hsv//swe |
| 650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Neurosciences0 (SwePub)301052 hsv//eng |
| 653 | a Alzheimer's disease | |
| 653 | a Molecular mechanisms | |
| 653 | a Biomarker discovery | |
| 653 | a Heterogeneity | |
| 653 | a Neuronal plasticity | |
| 653 | a Cerebrospinal fluid proteomics | |
| 653 | a amyloid precursor protein | |
| 653 | a cell-cycle progression | |
| 653 | a blood-brain-barrier | |
| 653 | a biomarkers | |
| 653 | a enrichment | |
| 653 | a adult | |
| 653 | a rest | |
| 653 | a wide | |
| 653 | a transcription | |
| 653 | a generation | |
| 653 | a Neurosciences & Neurology | |
| 653 | a Alzheimer's disease | |
| 700 | 1 | a Reus, L. M.u Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands4 aut |
| 700 | 1 | a Gobom, Johanu Gothenburg 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, Sweden4 aut0 (Swepub:gu)xgobjo |
| 700 | 1 | a Jansen, I.u Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University, Amsterdam, the Netherlands4 aut |
| 700 | 1 | a Dicks, E.u Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands4 aut |
| 700 | 1 | a Van der Lee, S. J.u Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands; Section Genomics of Neurodegenerative Diseases and Aging, Department of Clinical Genetics, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands,Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; AC Immune SA, Lausanne, Switzerland4 aut |
| 700 | 1 | a Tsolaki, M.u 1St Department of Neurology, AHEPA University Hospital, Thessaloniki, Makedonia, Greece4 aut |
| 700 | 1 | a Verhey, F. R. J.u Alzheimer Center Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands4 aut |
| 700 | 1 | a Popp, J.4 aut |
| 700 | 1 | a Martinez-Lage, P.u Fundación CITA-Alzhéimer Fundazioa, San Sebastian, Spain4 aut |
| 700 | 1 | a Vandenberghe, R.u Neurology Service, University Hospitals Leuven, Leuven, Belgium; Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium4 aut |
| 700 | 1 | a Lleo, A.u IIB-Sant Pau, Hospital de La Santa Creu I Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain4 aut |
| 700 | 1 | a Molinuevo, J. L.u Barcelonaβeta Brain Research Center (BBRC), Barcelona, Spain; Alzheimer's Disease Unit and Other Cognitive Disorders Unit, Hospital Clinic de Barcelona, Barcelona, Spain4 aut |
| 700 | 1 | a Engelborghs, S.u Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; Department of Neurology, UZ Brussel and Center for Neurosciences, Vrije Universiteit Brussel, Brussels, Belgium4 aut |
| 700 | 1 | a Freund-Levi, Yvonne,d 1956-u Örebro universitet,Institutionen för medicinska vetenskaper,Department of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Karolinska Institutet, Stockholm, Sweden; Department of Psychiatry at School of Medical Sciences, Örebro University, Örebro, Sweden4 aut0 (Swepub:oru)yfi |
| 700 | 1 | a Froelich, L.u Department of Geriatric Psychiatry, Zentralinstitut Für Seelische Gesundheit, University of Heidelberg, Mannheim, Germany4 aut |
| 700 | 1 | a Sleegers, K.u Complex Genetics Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium4 aut |
| 700 | 1 | a Dobricic, V.u Lübeck Interdisciplinary Platform for Genome Analytics, Institutes of Neurogenetics and Cardiogenetics, University of Lübeck, Lübeck, Germany4 aut |
| 700 | 1 | a Lovestone, S.u Jansen UK, High Wycombe, UK4 aut |
| 700 | 1 | a Streffer, J.4 aut |
| 700 | 1 | a Vos, S. J. B.u Alzheimer Center Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands4 aut |
| 700 | 1 | a Bos, I.u Alzheimer Center Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands4 aut |
| 700 | 1 | a Smit, A. B.u Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands4 aut |
| 700 | 1 | a Blennow, Kaj,d 1958u Gothenburg 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, Sweden4 aut0 (Swepub:gu)xbleka |
| 700 | 1 | a Scheltens, P.u Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands4 aut |
| 700 | 1 | a Teunissen, C. E.u Neurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam University Medical Centers (AUMC), Amsterdam Neuroscience, Netherlands4 aut |
| 700 | 1 | a Bertram, L.u Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Center for Lifespan Changes in Brain and Cognition, Dept. of Psychology, University of Oslo, Oslo, Norway4 aut |
| 700 | 1 | a Zetterberg, Henrik,d 1973u Gothenburg 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; Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK; Dementia Research Institute at UCL, London, UK4 aut0 (Swepub:gu)xzethe |
| 700 | 1 | a Tijms, B. M.u Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands4 aut |
| 700 | 1 | a Adni,, Adni,4 aut |
| 710 | 2 | a Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands; Alzheimer Center Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands; Department of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Karolinska Institutet, Stockholm, Swedenb Old Age Psychiatry, University Hospital Lausanne, Lausanne, Switzerland; Department of Geriatric Psychiatry, University Hospital of Psychiatry and University of Zürich, Zürich, Switzerland4 org |
| 773 | 0 | t Molecular Neurodegenerationd : Springer Science and Business Media LLCg 17:1q 17:1x 1750-1326 |
| 856 | 4 | u https://doi.org/10.1186/s13024-022-00521-3y Fulltext |
| 856 | 4 8 | u https://gup.ub.gu.se/publication/315298 |
| 856 | 4 8 | u https://doi.org/10.1186/s13024-022-00521-3 |
| 856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-98330 |
| 856 | 4 8 | u http://kipublications.ki.se/Default.aspx?queryparsed=id:149137006 |
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