Targeting butyrylcholinesterase for preclinical single photon emission computed tomography (SPECT) imaging of Alzheimer's disease

Drew R. DeBay1,2, George A. Reid1, Ian R. Pottie3,4, Earl Martin3, Chris V. Bowen2,5, Sultan Darvesh1,2,3,6
1Department of Medical Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada
2Biomedical Translational Imaging Centre, Halifax, Nova Scotia, Canada
3Department of Chemistry and Physics, Mount Saint Vincent University, Halifax, Nova Scotia, Canada
4Department of Chemistry Saint Mary’s, University Halifax, Nova Scotia, Canada
5Department of Radiology; Dalhousie University; Halifax, Nova Scotia, Canada.
6Department of Medicine, Dalhousie University, Halifax, Nova Scotia Canada

Tóm tắt

AbstractIntroductionDiagnosis of Alzheimer's disease (AD) in vivo, by molecular imaging of amyloid or tau, is constrained because similar changes can be found in brains of cognitively normal individuals. Butyrylcholinesterase (BChE), which becomes associated with these structures in AD, could elevate the accuracy of AD diagnosis by focusing on BChE pathology in the cerebral cortex, a region of scant BChE activity in healthy brain.MethodsN‐methylpiperidin‐4‐yl 4‐[123I]iodobenzoate, a BChE radiotracer, was injected intravenously into B6SJL‐Tg(APPSwFlLon, PSEN1∗M146 L∗L286 V) 6799Vas/Mmjax (5XFAD) mice and their wild‐type (WT) counterparts for comparative single photon emission computed tomography (SPECT) studies. SPECT, computed tomography (CT), and magnetic resonance imaging (MRI) enabled comparison of whole brain and regional retention of the BChE radiotracer in both mouse strains.ResultsRetention of the BChE radiotracer was consistently higher in the 5XFAD mouse than in WT, and differences were particularly evident in the cerebral cortex.DiscussionCerebral cortical BChE imaging with SPECT can distinguish 5XFAD mouse model from the WT counterpart.

Tài liệu tham khảo

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