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PIB is a non-specific imaging marker of amyloid-beta (Aβ) peptide-related cerebral amyloidosis

Lockhart, A. ; Lamb, J.R. ; Osredkar, T. ; Sue, L.I. ; Joyce, J.N. ; Ye, L. ; Libri, V. ; Leppert, D. ; Beach, T.G.

In: Brain, 2007, vol. 130, no. 10, p. 2607-2615

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    Titre
    • PIB is a non-specific imaging marker of amyloid-beta (Aβ) peptide-related cerebral amyloidosis
    Auteur
    • Lockhart, A.. GlaxoSmithKline, Clinical Science & Technology, CPDM and NGI-CEDD, NFSP North, Third Avenue, Harlow, Essex, CM19 5AW, UK, Department of Veterinary Clinical Studies, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Veterinary Centre, Roslin, Midlothian EH25 9RG, UK, Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ 85372, Maricopa Integrated Health System, 2601 East Roosevelt Street, Phoenix, AZ 85008, USA and Department of Neurology, University Hospital Basel, Petersgraben 4, CH-4031 Basel, Switzerland
    • Lamb, J.R.. GlaxoSmithKline, Clinical Science & Technology, CPDM and NGI-CEDD, NFSP North, Third Avenue, Harlow, Essex, CM19 5AW, UK, Department of Veterinary Clinical Studies, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Veterinary Centre, Roslin, Midlothian EH25 9RG, UK, Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ 85372, Maricopa Integrated Health System, 2601 East Roosevelt Street, Phoenix, AZ 85008, USA and Department of Neurology, University Hospital Basel, Petersgraben 4, CH-4031 Basel, Switzerland
    • Osredkar, T.. GlaxoSmithKline, Clinical Science & Technology, CPDM and NGI-CEDD, NFSP North, Third Avenue, Harlow, Essex, CM19 5AW, UK, Department of Veterinary Clinical Studies, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Veterinary Centre, Roslin, Midlothian EH25 9RG, UK, Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ 85372, Maricopa Integrated Health System, 2601 East Roosevelt Street, Phoenix, AZ 85008, USA and Department of Neurology, University Hospital Basel, Petersgraben 4, CH-4031 Basel, Switzerland
    • Sue, L.I.. GlaxoSmithKline, Clinical Science & Technology, CPDM and NGI-CEDD, NFSP North, Third Avenue, Harlow, Essex, CM19 5AW, UK, Department of Veterinary Clinical Studies, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Veterinary Centre, Roslin, Midlothian EH25 9RG, UK, Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ 85372, Maricopa Integrated Health System, 2601 East Roosevelt Street, Phoenix, AZ 85008, USA and Department of Neurology, University Hospital Basel, Petersgraben 4, CH-4031 Basel, Switzerland
    • Joyce, J.N.. GlaxoSmithKline, Clinical Science & Technology, CPDM and NGI-CEDD, NFSP North, Third Avenue, Harlow, Essex, CM19 5AW, UK, Department of Veterinary Clinical Studies, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Veterinary Centre, Roslin, Midlothian EH25 9RG, UK, Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ 85372, Maricopa Integrated Health System, 2601 East Roosevelt Street, Phoenix, AZ 85008, USA and Department of Neurology, University Hospital Basel, Petersgraben 4, CH-4031 Basel, Switzerland
    • Ye, L.. GlaxoSmithKline, Clinical Science & Technology, CPDM and NGI-CEDD, NFSP North, Third Avenue, Harlow, Essex, CM19 5AW, UK, Department of Veterinary Clinical Studies, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Veterinary Centre, Roslin, Midlothian EH25 9RG, UK, Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ 85372, Maricopa Integrated Health System, 2601 East Roosevelt Street, Phoenix, AZ 85008, USA and Department of Neurology, University Hospital Basel, Petersgraben 4, CH-4031 Basel, Switzerland
    • Libri, V.. GlaxoSmithKline, Clinical Science & Technology, CPDM and NGI-CEDD, NFSP North, Third Avenue, Harlow, Essex, CM19 5AW, UK, Department of Veterinary Clinical Studies, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Veterinary Centre, Roslin, Midlothian EH25 9RG, UK, Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ 85372, Maricopa Integrated Health System, 2601 East Roosevelt Street, Phoenix, AZ 85008, USA and Department of Neurology, University Hospital Basel, Petersgraben 4, CH-4031 Basel, Switzerland
    • Leppert, D.. GlaxoSmithKline, Clinical Science & Technology, CPDM and NGI-CEDD, NFSP North, Third Avenue, Harlow, Essex, CM19 5AW, UK, Department of Veterinary Clinical Studies, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Veterinary Centre, Roslin, Midlothian EH25 9RG, UK, Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ 85372, Maricopa Integrated Health System, 2601 East Roosevelt Street, Phoenix, AZ 85008, USA and Department of Neurology, University Hospital Basel, Petersgraben 4, CH-4031 Basel, Switzerland
    • Beach, T.G.. GlaxoSmithKline, Clinical Science & Technology, CPDM and NGI-CEDD, NFSP North, Third Avenue, Harlow, Essex, CM19 5AW, UK, Department of Veterinary Clinical Studies, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Veterinary Centre, Roslin, Midlothian EH25 9RG, UK, Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ 85372, Maricopa Integrated Health System, 2601 East Roosevelt Street, Phoenix, AZ 85008, USA and Department of Neurology, University Hospital Basel, Petersgraben 4, CH-4031 Basel, Switzerland
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Brain, 2007, vol. 130, no. 10, p. 2607-2615. Oxford University Press
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:290676
    Summary
    The in vivo imaging probe [11C]-PIB (Pittsburgh Compound B, N-methyl[11C]2-(4′-methylaminophenyl-6-hydroxybenzathiazole) is under evaluation as a key imaging tool in Alzheimer's disease (AD) and to date has been assumed to bind with high affinity and specificity to the amyloid structures associated with classical plaques (CPs), one of the pathological hallmarks of the disease. However, no studies have systematically investigated PIB binding to human neuropathological brain specimens at the tracer concentrations achieved during in vivo imaging scans. Using a combination of autoradiography and histochemical techniques, we demonstrate that PIB, in addition to binding CPs clearly delineates diffuse plaques and cerebrovascular amyloid angiopathy (CAA). The interaction of PIB with CAA was not fully displaceable and this may be linked to the apolipoprotein E-ε4 allele. PIB was also found to label neurofibrillary tangles, although the overall intensity of this binding was markedly lower than that associated with the amyloid-beta (Aβ) pathology. The data provide a molecular explanation for PIB's limited specificity in diagnosing and monitoring disease progression in AD and instead indicate that the ligand is primarily a non-specific marker of Aβ-peptide related cerebral amyloidosis