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The Journal of Neuroscience, September 26, 2007, 27(39):10365-10371; doi:10.1523/JNEUROSCI.0630-07.2007

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Neurobiology of Disease
In Vitro Characterization of Pittsburgh Compound-B Binding to Lewy Bodies

Michelle T. Fodero-Tavoletti,^1,2,4 David P. Smith,^1,4 Catriona A. McLean,⁵ Paul A. Adlard,⁴ Kevin J. Barnham,^1,2,4 Lisa E. Foster,¹ Laura Leone,¹ Keyla Perez,^1,2,4 Mikhalina Cortés,⁴ Janetta G. Culvenor,^1,3,4 Qiao-Xin Li,^1,4 Katrina M. Laughton,^1,4 Christopher C. Rowe,⁶ Colin L. Masters,^1,4 Roberto Cappai,^1,2,4 and Victor L. Villemagne^1,4,6

¹Department of Pathology, ²Bio21 Institute, and ³Centre for Neuroscience, The University of Melbourne, Melbourne, Victoria 3010, Australia, ⁴The Mental Health Research Institute of Victoria, Parkville, Victoria 3052, Australia, ⁵Department of Anatomical Pathology, Alfred Hospital, Prahran, Victoria 3181, Australia, and ⁶Centre for PET, Austin Hospital, Heidelberg, Victoria 3084, Australia

Correspondence should be addressed to Victor L. Villemagne, Department of Nuclear Medicine, Centre for PET, Austin Hospital, 145 Studley Road, Heidelberg, Victoria 3084, Australia. Email: villemagne{at}petnm.unimelb.edu.au

Dementia with Lewy bodies (DLB) is pathologically characterized by the presence of -synuclein-containing Lewy bodies within the neocortical, limbic, and paralimbic regions. Like Alzheimer's disease (AD), Aß plaques are also present in most DLB cases. The contribution of Aß to the development of DLB is unclear. [¹¹C]-Pittsburgh compound B ([¹¹C]-PIB) is a thioflavin-T derivative that has allowed in vivo Aß burden to be quantified using positron emission tomography (PET). [¹¹C]-PIB PET studies have shown similar high cortical [¹¹C]-PIB binding in AD and DLB subjects. To establish the potential binding of PIB to -synuclein in DLB patients, we characterized the in vitro binding of PIB to recombinant human -synuclein and DLB brain homogenates. Analysis of the in vitro binding studies indicated that [³H]-PIB binds to -synuclein fibrils but with lower affinity than that demonstrated/reported for Aß_1–42 fibrils. Furthermore, [³H]-PIB was observed to bind to Aß plaque-containing DLB brain homogenates but failed to bind to DLB homogenates that were Aß plaque-free ("pure DLB"). Positive PIB fluorescence staining of DLB brain sections colocalized with immunoreactive Aß plaques but failed to stain Lewy bodies. Moreover, image quantification analysis suggested that given the small size and low density of Lewy bodies within the brains of DLB subjects, any contribution of Lewy bodies to the [¹¹C]-PIB PET signal would be negligible. These studies indicate that PIB retention observed within the cortical gray matter regions of DLB subjects in [¹¹C]-PIB PET studies is largely attributable to PIB binding to Aß plaques and not Lewy bodies.

Key words: -synuclein; PET; Aß; DLB; Alzheimer's disease; amyloid

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Received Feb. 12, 2007; revised July 19, 2007; accepted July 20, 2007.

Correspondence should be addressed to Victor L. Villemagne, Department of Nuclear Medicine, Centre for PET, Austin Hospital, 145 Studley Road, Heidelberg, Victoria 3084, Australia. Email: villemagne{at}petnm.unimelb.edu.au

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