靶向丁酰胆碱酯酶用于阿尔茨海默病的临床前单光子发射计算机断层扫描（SPECT）成像

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

作者信息

DeBay Drew R, Reid George A, Pottie Ian R, Martin Earl, Bowen Chris V, Darvesh Sultan

机构信息

Department of Medical Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada.

Biomedical Translational Imaging Centre, Halifax, Nova Scotia, Canada.

出版信息

Alzheimers Dement (N Y). 2017 Feb 24;3(2):166-176. doi: 10.1016/j.trci.2017.01.005. eCollection 2017 Jun.

INTRODUCTION

Diagnosis of Alzheimer's disease (AD) , 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.

METHODS

-methylpiperidin-4-yl 4-[I]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.

RESULTS

Retention of the BChE radiotracer was consistently higher in the 5XFAD mouse than in WT, and differences were particularly evident in the cerebral cortex.

DISCUSSION

Cerebral cortical BChE imaging with SPECT can distinguish 5XFAD mouse model from the WT counterpart.

引言

通过淀粉样蛋白或tau蛋白的分子成像来诊断阿尔茨海默病（AD）存在局限性，因为在认知正常个体的大脑中也能发现类似变化。丁酰胆碱酯酶（BChE）在AD中与这些结构相关联，通过聚焦于大脑皮层中的BChE病理学（健康大脑中该区域BChE活性较低），可能会提高AD诊断的准确性。

方法

将一种BChE放射性示踪剂4-[I]碘苯甲酸甲酯-甲基哌啶-4-基静脉注射到B6SJL-Tg(APPSwFlLon,PSEN1∗M146L∗L286V)6799Vas/Mmjax（5XFAD）小鼠及其野生型（WT）对照小鼠体内，进行比较性单光子发射计算机断层扫描（SPECT）研究。SPECT、计算机断层扫描（CT）和磁共振成像（MRI）能够比较两种小鼠品系全脑和局部对BChE放射性示踪剂的摄取情况。