alexa K16ApoE Enhances A <em>andbeta;</em>-associated 11C-PiB Deposition and PET Signal in <em>APP</em>/ PS1 Transgenic Mice | OMICS International| Abstract
ISSN: 2161-0460

Journal of Alzheimers Disease & Parkinsonism
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  • Research Article   
  • J Alzheimers Dis Parkinsonism 2019, Vol 9(3): 468

K16ApoE Enhances A β-associated 11C-PiB Deposition and PET Signal in APP/ PS1 Transgenic Mice

Brown DA1*#, Sarkar G2#, Decklever TD3, Curran GL3, Sarkar AJ3, Schmeichel AM4, Swaminathan SK5, Kandimala KK5, Jenkins RB2, Burns TC5 and Lowe VJ3
1Departments of Neurosurgery, Mayo Clinic, Rochester, MN, USA
2Departments of Experimental Pathology, Mayo Clinic, Rochester, MN, USA
3Departments of Nuclear Medicine, Mayo Clinic, Rochester, MN, USA
4Departments of Neurology, Mayo Clinic, Rochester, MN, USA
5Department of Pharmaceutics and Brain Barriers Research Center, University of Minnesota, Minneapolis, MN, USA
#Contributed equally to this work
*Corresponding Author : Brown DA MD, PhD, Department of Neurosurgery, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905, USA, Tel: 507-255- 5831, Email: [email protected]

Received Date: May 29, 2019 / Accepted Date: Jun 13, 2019 / Published Date: Jun 20, 2019

Abstract

Objective: Transgenic mouse models are central to the study of Alzheimer’s disease and aid in elucidating the underlying pathophysiology. Mouse models also provide a system in which to test potential therapeutic strategies. PET imaging plays a central clinical role in diagnosing human cases of Alzheimer’s disease but has had variable performance in mouse models. We investigated the potential role of the K16ApoE carrier peptide to enhance delivery of a radiolabeled PET imaging tracer, 11C-PiB and assess whether this corresponds to improved sensitivity of the PET modality in APP/PS1 transgenic mice.

Methods: Brain-delivery of 11C-PiB was accomplished by sequential bolus injections of K16ApoE and 11C-PiB via femoral vein injections. Distribution of 11C-PiB to the brain and heart was quantified via dynamic PET/CT imaging and digital autoradiography.

Results: K16ApoE carrier peptide increased the brain uptake of 11C-PiB in both wild-type and APP/PS1 mice. Administration of K16ApoE increased the PET standard uptake value of 11C-PiB at 5 minutes in WT mice from 1.132 to 2.963 (p=0.006) and in APP/PS1 mice from 0.842 to 3.268 (p=0.016). Enhancement peaked at 5 minutes. Binding was reversible as demonstrable by Logan plots with similarly increased kinetics in both WT and APP/PS1 mice. The absolute values were higher in APP/PS1 mice suggesting increased retention. The increased retention in APP/PS1 mice was consistent with specific binding to Aβ plaques as unlabeled PiB showed competitive reduction of 11C-PiB signal retention.

Conclusion: K16ApoE-mediates enhancement of 11C-PiB signal in APP/PS1 mice brains with increase in the PET sensitivity. There is increased uptake kinetics in both WT and APP/PS1 mice with specific retention due to Aβ plaque binding in the latter. This improved sensitivity of PET scanning in the APP/PS1 transgenic mouse model. Such enhanced delivery of this PET tracer has implications for development and testing of new hypotheses and the efficacy of novel therapeutic paradigms.

Keywords: Alzheimer’s disease; 11C-PiB, PET; Blood-brain barrier; Carrier peptide; Digital autoradiography; DVR; RRT; Mouse model

Citation: Brown DA, Sarkar G, Decklever TD, Curran GL, Sarkar AJ, et al. (2019) K16ApoE Enhances Aβ-associated 11C-PiB Deposition and PET Signal in APP/ PS1 Transgenic Mice. J Alzheimers Dis Parkinsonism 9: 468.

Copyright: © 2019 Brown DA, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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