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Author Notes:

Correspondence: Lary C. Walker and Rebecca F. Rosen, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, GA 30329, USA; Email: lary.walker@emory.edu, Email: rfrosen@emory.edu; Phone: 404-727-7779; Fax: 404-727-5289

Acknowledgments: We thank M. Paul Murphy for helpful discussions, and Jean-Francois Pare, Carolyn Suwyn, Elaine Pranski and Aaron Farberg for excellent technical assistance.


Research Funding:

This work was supported by RR-00165, PO1AG026423, P50AG025688, the Woodruff Foundation and the Emory University Research Committee.


  • Alzheimer
  • amyloid-beta
  • cerebral amyloid angiopathy
  • diagnosis
  • imaging
  • PIB
  • senile plaques

Deficient high-affinity binding of Pittsburgh compound B in a case of Alzheimer’s disease


Journal Title:

Acta Neuropathologica


Volume 119, Number 2


, Pages 221-233

Type of Work:

Article | Post-print: After Peer Review


Radiolabeled Pittsburgh compound B (PIB) is a benzothiazole imaging agent that usually binds with high affinity, specificity, and stoichiometry to cerebral β-amyloid (Aβ) in patients with Alzheimer’s disease. Among a cohort of ten AD subjects examined postmortem, we describe a case of idiopathic, end-stage Alzheimer’s disease with heavy Aβ deposition yet substantially diminished high-affinity binding of 3H-PIB to cortical homogenates and unfixed cryosections. Cortical tissue samples were analyzed by immunohistochemistry, electron microscopy, ELISA, immunoblotting, MALDI-TOF mass spectrometry, in vitro 3H-PIB binding and 3H-PIB autoradiography. The PIB-refractory subject met the histopathological criteria for AD. However, cortical tissue from this case contained more vascular β-amyloidosis, higher levels of insoluble Aβ40 and Aβ42, and a higher ratio of Aβ40:Aβ42 than did tissue from the nine comparison AD cases. Furthermore, cerebral Aβ from the PIB-refractory subject displayed an unusual distribution of low- and high-molecular weight Aβ oligomers, as well as a distinct pattern of N- and C-terminally truncated Aβ peptides in both the soluble and insoluble cortical extracts. Genetically, the patient was apolipoprotein-Eε4 heterozygous, and exhibited no known AD-associated mutations in the genes of the β-amyloid precursor protein, presenilin-1 or presenilin-2. Our findings suggest that PIB may differentially recognize polymorphic forms of multimeric Aβ in humans with Alzheimer’s disease. In addition, while the prevalence of PIB-refractory cases in the general AD population remains to be determined, the paucity of high-affinity binding sites in this AD case cautions that minimal PIB retention in positron-emission tomography scans of demented patients may not always rule out the presence of Alzheimer-type Aβ pathology.

Copyright information:

© Springer-Verlag 2009

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