Mount St. Vincent University
Chemistry and Physics

Author Of 1 Presentation

Pathogenesis – Immunology Poster Presentation

P0968 - Imaging butyrylcholinesterase in multiple sclerosis (ID 1005)

Speakers
Presentation Number
P0968
Presentation Topic
Pathogenesis – Immunology

Abstract

Background

Multiple sclerosis (MS) is a chronic immune-mediated inflammatory and neuro-degenerative disease of the central nervous system. The cholinergic system is dysregulated in MS, with alterations in cholinesterase activity, particularly an increase in butyrylcholinesterase (BChE) activity, which correlates with activated microglia in white matter lesions and adjacent normal-appearing white matter (NAWM). Magnetic resonance imaging (MRI) is used to confirm the diagnosis of MS, and to monitor disease activity and treatment response. Although it is the gold standard in MS, MRI lacks the ability to detect subtle changes to NAWM, and more sensitive imaging modalities are required. Molecular imaging agents targeting BChE have shown promise in other neurodegenerative disorders, and may have utility in detecting changes to NAWM in MS.

Objectives

The purpose of this study was to further characterize changes in the cholinergic system in MS pathology, and to explore the potential utility of BChE imaging agents as potential diagnostic and therapeutic agents in MS.

Methods

Representative samples from post-mortem brain tissues of individuals with MS and healthy controls were compared. Cortical and white matter lesions were identified using myelin staining, and lesions were classified based on microglial activation patterns. Adjacent brain sections were used for cholinesterase histochemistry and in vitro autoradiography using phenyl 4-123[I]-iodophenylcarbamate (123I-PIP), a previously described small molecule cholinesterase-binding imaging agent.

Results

BChE activity is positively correlated with microglial activation in white matter MS lesions. There is no alteration in cholinesterase activity in cortical MS lesions. 123I-PIP autoradiography revealed uptake of radioactivity in normal white matter, absence of radioactivity within demyelinated MS lesions and variable uptake of radioactivity in adjacent NAWM.

Conclusions

BChE imaging agents have the potential to detect MS lesions and subtle pathology in NAWM in MS. This modality could eventually supplement current imaging methods to facilitate early diagnosis and treatment monitoring.

Disclosures: This work has been submitted for consideration of publication in the journal Molecular Imaging and Biology, and at this time a decision is pending.

Ref: Imaging Butyrylcholinesterase in Multiple Sclerosis. Thorne MWD; Cash MK; Reid GA; Burley DE; Luke D; Pottie IR; Darvesh S. Molecular Imaging and Biology (Submited June, 2020)

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