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pubmed, article, google, scholar, alzheimers, disease, cas, csf, central, biomarkers, fluid, levels, tau, cerebrospinal, patients, plasma, biomarker, protein, study, neurol, cognitive, brain, amyloid, clinical, studies, research, blennow, mci, pathology, αsynuclein, dementia, zetterberg, diagnosis, dis, httpsdoiorgs, neurodegenerative, potential, controls, early, increased, found, alzheimer, dement, diseases, ttau, bace, synaptic, subjects, impairment, httpsdoiorgjad,

Topics {✒️}

eu/docs/en_gb/document_library/regulatory_and_procedural_guideline/2011/12/wc500118365 eu/docs/en_gb/document_library/scientific_guideline/2018/02/wc500244609 gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm267449 gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm596728 int/mediacentre/factsheets/fs362/en/ cerebro-spinal-fluid related biomarkers c-terminally truncated alpha-synuclein storage-dependent pre-analytical variability article download pdf amyloid-β-induced cell death alpha-synuclein oligomers-neurotoxic molecules n-methyl-d-aspartate cerebrospinal fluid tau/β-amyloid mismatch—high p-tau accompanied tnf-α converting enzyme α-synuclein pathology α-synuclein single-molecule fluorescence microscopy n-truncated abeta peptides quantitative susceptibility mapping clinical alzheimer’s-type dementia csf aβ1-42/aβ1-40 ratio cerebrospinal fluid aβeta42/aβeta40 transforming growth factor-β hypoxia/ischemia activate processing biomarker-guided classification system tumour necrosis factor evaluating amyloid-β oligomers phospho-tau/total tau ratio alpha-synuclein rt-quic increased protein-conjugated acrolein cerebrospinal fluid amyloid-β biomarker-guided classification scheme standardize csf pre-analytics amyloid-β degradation pattern post-translationally modified fragments pathological α-synuclein exacerbates relapsing-remitting multiple sclerosis csf pre-analytics consortium jack cr jr aβ-plaque deposition equivalent fluid-based surrogate biomarkers fluid-based α-synuclein circulating brain-enriched micrornas facilitate pre-symptomatic diagnosis accurately predict aβ-positivity end-specific aβ monoclonals ante-mortem cognitive status remaining pre-analytical factors mass-spectrometry-based method natalizumab-treated multiple sclerosis

Questions {❓}

• Jackson K, Barisone GA, Diaz E, Jin LW, DeCarli C, Despa F (2013) Amylin deposition in the brain: a second amyloid in Alzheimer disease?
• Steardo L Jr, Bronzuoli MR, Iacomino A, Esposito G, Steardo L, Scuderi C (2015) Does neuroinflammation turn on the flame in Alzheimer’s disease?
• Willemse E, van Uffelen K, Brix B, Engelborghs S, Vanderstichele H, Teunissen C (2017) How to handle adsorption of cerebrospinal fluid amyloid β (1-42) in laboratory practice?

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         headline:Current state of Alzheimer’s fluid biomarkers
         description:Alzheimer’s disease (AD) is a progressive neurodegenerative disease with a complex and heterogeneous pathophysiology. The number of people living with AD is predicted to increase; however, there are no disease-modifying therapies currently available and none have been successful in late-stage clinical trials. Fluid biomarkers measured in cerebrospinal fluid (CSF) or blood hold promise for enabling more effective drug development and establishing a more personalized medicine approach for AD diagnosis and treatment. Biomarkers used in drug development programmes should be qualified for a specific context of use (COU). These COUs include, but are not limited to, subject/patient selection, assessment of disease state and/or prognosis, assessment of mechanism of action, dose optimization, drug response monitoring, efficacy maximization, and toxicity/adverse reactions identification and minimization. The core AD CSF biomarkers Aβ42, t-tau, and p-tau are recognized by research guidelines for their diagnostic utility and are being considered for qualification for subject selection in clinical trials. However, there is a need to better understand their potential for other COUs, as well as identify additional fluid biomarkers reflecting other aspects of AD pathophysiology. Several novel fluid biomarkers have been proposed, but their role in AD pathology and their use as AD biomarkers have yet to be validated. In this review, we summarize some of the pathological mechanisms implicated in the sporadic AD and highlight the data for several established and novel fluid biomarkers (including BACE1, TREM2, YKL-40, IP-10, neurogranin, SNAP-25, synaptotagmin, α-synuclein, TDP-43, ferritin, VILIP-1, and NF-L) associated with each mechanism. We discuss the potential COUs for each biomarker.
         datePublished:2018-11-28T00:00:00Z
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      headline:Current state of Alzheimer’s fluid biomarkers
      description:Alzheimer’s disease (AD) is a progressive neurodegenerative disease with a complex and heterogeneous pathophysiology. The number of people living with AD is predicted to increase; however, there are no disease-modifying therapies currently available and none have been successful in late-stage clinical trials. Fluid biomarkers measured in cerebrospinal fluid (CSF) or blood hold promise for enabling more effective drug development and establishing a more personalized medicine approach for AD diagnosis and treatment. Biomarkers used in drug development programmes should be qualified for a specific context of use (COU). These COUs include, but are not limited to, subject/patient selection, assessment of disease state and/or prognosis, assessment of mechanism of action, dose optimization, drug response monitoring, efficacy maximization, and toxicity/adverse reactions identification and minimization. The core AD CSF biomarkers Aβ42, t-tau, and p-tau are recognized by research guidelines for their diagnostic utility and are being considered for qualification for subject selection in clinical trials. However, there is a need to better understand their potential for other COUs, as well as identify additional fluid biomarkers reflecting other aspects of AD pathophysiology. Several novel fluid biomarkers have been proposed, but their role in AD pathology and their use as AD biomarkers have yet to be validated. In this review, we summarize some of the pathological mechanisms implicated in the sporadic AD and highlight the data for several established and novel fluid biomarkers (including BACE1, TREM2, YKL-40, IP-10, neurogranin, SNAP-25, synaptotagmin, α-synuclein, TDP-43, ferritin, VILIP-1, and NF-L) associated with each mechanism. We discuss the potential COUs for each biomarker.
      datePublished:2018-11-28T00:00:00Z
      dateModified:2018-11-28T00:00:00Z
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      pageEnd:853
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         Amyloid
         Biomarker
         Blood
         Cerebrospinal fluid
         Tau
         Pathology
         Neurosciences
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         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00401-018-1932-x/MediaObjects/401_2018_1932_Fig1_HTML.png
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      address:
         name:Departments of Epidemiology and Neurology, Mayo Clinic, Rochester, USA
         type:PostalAddress
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         name:Biomarkers, Biogen, Cambridge, USA
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            address:
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            address:
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            address:
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            type:Organization
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            address:
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            address:
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               type:PostalAddress
            type:Organization
      name:Leslie M. Shaw
      affiliation:
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            address:
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               type:PostalAddress
            type:Organization
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      affiliation:
            name:Clinical Development Neurology, AbbVie
            address:
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               type:PostalAddress
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      name:Gary Tong
      affiliation:
            name:Lundbeck
            address:
               name:Lundbeck, Deerfield, USA
               type:PostalAddress
            type:Organization
      name:John Q. Trojanowski
      affiliation:
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            address:
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               type:PostalAddress
            type:Organization
      name:Henrik Zetterberg
      affiliation:
            name:The Sahlgrenska Academy at the University of Gothenburg
            address:
               name:Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
               type:PostalAddress
            type:Organization
            name:Sahlgrenska University Hospital
            address:
               name:Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal Campus, Sahlgrenska University Hospital, Mölndal, Sweden
               type:PostalAddress
            type:Organization
            name:UCL Institute of Neurology
            address:
               name:Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK
               type:PostalAddress
            type:Organization
            name:UK Dementia Research Institute at UCL
            address:
               name:UK Dementia Research Institute at UCL, London, UK
               type:PostalAddress
            type:Organization
      name:Kaj Blennow
      affiliation:
            name:The Sahlgrenska Academy at the University of Gothenburg
            address:
               name:Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
               type:PostalAddress
            type:Organization
            name:Sahlgrenska University Hospital
            address:
               name:Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal Campus, Sahlgrenska University Hospital, Mölndal, Sweden
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:BarcelonaBeta Brain Research Center, Fundació Pasqual Maragall, Universitat Pompeu Fabra, Barcelona, Spain
      name:Unidad de Alzheimer y otros trastornos cognitivos, Hospital Clinic-IDIBAPS, Barcelona, Spain
      name:Melbourne Dementia Research Centre, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia
      name:Roche Centralised and Point of Care Solutions, Roche Diagnostics International, Rotkreuz, Switzerland
      name:Neuroscience Therapeutic Area Unit, Takeda Development Centre Americas Ltd, Cambridge, USA
      name:Genentech, A Member of the Roche Group, Basel, Switzerland
      name:Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, USA
      name:Department of Neurology, Washington University in St. Louis, St. Louis, USA
      name:AXA Research Fund and Sorbonne University Chair, Paris, France
      name:Sorbonne University, GRC No 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Paris, France
      name:Brain and Spine Institute (ICM), INSERM U 1127, CNRS UMR 7225, Paris, France
      name:Department of Neurology, Institute of Memory and Alzheimer’s Disease (IM2A), Pitié-Salpêtrière Hospital, AP-HP, Paris, France
      name:Departments of Epidemiology and Neurology, Mayo Clinic, Rochester, USA
      name:Biomarkers, Biogen, Cambridge, USA
      name:Department of Pharmacology and Neuroscience; Institute for Healthy Aging, University of North Texas Health Science Center, Fort Worth, USA
      name:Department of Neurology and Alzheimer Center, VU University Medical Center, Amsterdam, The Netherlands
      name:Roche Innovation Center Basel, F. Hoffmann-La Roche, Basel, Switzerland
      name:Department of Pathology and Laboratory Medicine, and Center for Neurodegenerative Disease Research, University of Pennsylvania, Philadelphia, USA
      name:Clinical Development Neurology, AbbVie, North Chicago, USA
      name:Lundbeck, Deerfield, USA
      name:Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, USA
      name:Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
      name:Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal Campus, Sahlgrenska University Hospital, Mölndal, Sweden
      name:Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK
      name:UK Dementia Research Institute at UCL, London, UK
      name:Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
      name:Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal Campus, Sahlgrenska University Hospital, Mölndal, Sweden

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