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

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 associ...

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Bibliographic Details
Published in:	Brain (London, England : 1878) Vol. 130; no. 10; pp. 2607 - 2615
Main Authors:	Lockhart, A., Lamb, J.R., Osredkar, T., Sue, L.I., Joyce, J.N., Ye, L., Libri, V., Leppert, D., Beach, T.G.
Format:	Journal Article
Language:	English
Published:	Oxford Oxford University Press 01-10-2007 Oxford Publishing Limited (England)
Subjects:	Alzheimer Disease - diagnostic imaging Alzheimer Disease - metabolism Alzheimer Disease - pathology Alzheimer's disease amyloid Amyloid beta-Peptides - metabolism Aniline Compounds - metabolism Biological and medical sciences Biomarkers - metabolism Brain - metabolism Brain - pathology Carbon Radioisotopes Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Humans imaging Medical sciences Neurology PIB positron emission tornography Positron-Emission Tomography - methods Thiazoles - metabolism Vascular diseases and vascular malformations of the nervous system positron emission tornography PIB amyloid Alzheimer's disease imaging Nervous system diseases Peptides Alzheimer disease Central nervous system Metabolic diseases Enzymopathy Protein Cerebral disorder Central nervous system disease Degenerative disease Amyloid Amyloidosis Positron emission tomography Emission tomography
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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.
Bibliography:	istex:4280E453A53733F2A053515138C768CB3801BD33 ark:/67375/HXZ-GBQSMZD4-3 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0006-8950 1460-2156
DOI:	10.1093/brain/awm191