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Brain Advance Access published online on August 13, 2007
Brain, doi:10.1093/brain/awm191
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© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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

A. Lockhart1, J.R. Lamb2, T. Osredkar3, L.I. Sue3, J.N. Joyce4, L. Ye1, V. Libri1, D. Leppert5 and T.G. Beach3

1GlaxoSmithKline, Clinical Science & Technology, CPDM and NGI-CEDD, NFSP North, Third Avenue, Harlow, Essex, CM19 5AW, UK, 2Department of Veterinary Clinical Studies, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Veterinary Centre, Roslin, Midlothian EH25 9RG, UK, 3Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ 85372, 4Maricopa Integrated Health System, 2601 East Roosevelt Street, Phoenix, AZ 85008, USA and 5Department of Neurology, University Hospital Basel, Petersgraben 4, CH-4031 Basel, Switzerland

Correspondence to: A. Lockhart, Clinical Science & Technology, Neurology-CPDM, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK E-mail: Andrew.2.Lockhart{at}gsk.com

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-{varepsilon}4 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 (Aß) 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 Aß-peptide related cerebral amyloidosis.

Key Words: PIB; amyloid; Alzheimer's disease; positron emission tornography; imaging

Abbreviations: AD, Alzheimer's disease; ApoE, apolipoprotein E; Aß, amyloid-beta peptide; BTA-1, 2-(4'-methylaminophenyl)benzothiazole; CAA, cerebrovascular amyloid angiopathy; CAA-NDB, CAA-associated non-displaceable binding; CPs, classical plaques; DLB, dementia with Lewy bodies; DPs, diffuse plaques; ECX, entorhinal cortex; FDDNP, 2-(1-{6-[(2-fluoroethyl(methyl)amino]-2-naphthyl}ethylidene)malononitrile; FTD, frontotemporal dementia; MFG, mid-frontal gyrus; NFTs, neurofibrillary tangles; NDB, non-displaceable binding; OCL, occipital lobe; PET, positron emission tomography; PIB, Pittsburgh Compound-B (2-[4'-(methylamino)phenyl]-6-hydroxybenzothiazole); rCMRglc, regional cerebral glucose metabolism rate; SB13, 4-N-methylamino-4'-hydroxystilbene; SPL, superior parietal lobe; SPs, senile plaques

Received April 27, 2007. Revised July 12, 2007. Accepted July 23, 2007.


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