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Roy N. Alcalay, M.D.
"Why do some people who carry genetic mutations associated with Parkinson’s disease (PD) never develop PD while others do?" asks Roy N. Alcalay, M.D., a postdoctoral fellow at the Center for Parkinson’s Disease and Other Movement Disorders...
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In vitro characterisation of BF227 binding to alpha-synuclein/Lewy bodies.
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Eur J Pharmacol 2009 Jul;
Authors: Michelle T Fodero-Tavoletti, Rachel S Mulligan, Nobuyuki Okamura, Shozo Furumoto, Christopher C Rowe, Yukitsuka Kudo, Colin L Masters, Roberto Cappai, Kazuhiko Yanai, Victor L Villemagne
Department of Pathology, The University of Melbourne, VIC, Australia; Bio21 Molecular and Biotechnology Institute, The University of Melbourne, VIC, Australia; The Mental Health Research Institute of Victoria, Tohoku University, Sendai, Japan.
Abeta plaques are a pathological hallmark of Alzheimer's disease and a current target for positron emission tomography (PET) imaging agents. Whilst [(11)C]-PiB is currently the most widely used PET ligand in clinic, a novel family of benzoxazole compounds have shown promise as Abeta imaging agents; particularly BF227. We characterised the in vitro binding of [(18)F]-BF227 toward alpha-synuclein to address its selectivity for Abeta pathology, to establish whether [(18)F]-BF227 binds to alpha-synuclein/Lewy bodies, in addition to Abeta plaques. In vitro [(18)F]-BF227 saturation studies were conducted with 200 nM alpha-synuclein or Abeta(1-42) fibrils or 100 mug of Alzheimer's disease, pure dementia with Lewy bodies or control brain homogenates. Non-specific binding was established with PiB (1 muM). In vitro binding studies indicated that [(18)F]-BF227 binds with high affinity to two binding sites on Abeta(1-42) fibrils (K(D1) = 1.31 and K(D2) = 80 nM, respectively) and to one class of binding sites on alpha-synuclein fibrils (K(D) = 9.63nM). [(18)F]-BF227 bound to Abeta-containing Alzheimer's disease brain (K(D) = 25 +/- 0.5 nM), but failed to bind to Abeta-free dementia with Lewy bodies or age-matched control homogenates. Moreover, BF227 labelled both Abeta plaques and Lewy bodies in immunohistochemical/fluorescence analysis of human Alzheimer's disease and Parkinson's disease brain sections, respectively. This study suggests that [(18)F]-BF227 is not Abeta-selective. Evaluation of BF227 as a potential biomarker for Parkinson's disease is warranted.
PMID: 19576880 [PubMed - as supplied by publisher]
