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

Diagnosis 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...

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Published inAlzheimer's & dementia : translational research & clinical interventions Vol. 3; no. 2; pp. 166 - 176
Main Authors DeBay, Drew R., Reid, George A., Pottie, Ian R., Martin, Earl, Bowen, Chris V., Darvesh, Sultan
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 01.06.2017
Elsevier
Subjects
123Iodine
Acetylcholinesterase
Alzheimer mouse model with 5 familial mutations
Alzheimer's disease
Butyrylcholinesterase
Molecular imaging
Neuroimaging
Single-photon emission computed tomography
Molecular imaging
Neuroimaging
Alzheimer mouse model with 5 familial mutations
Single-photon emission computed tomography
123Iodine
Butyrylcholinesterase
Acetylcholinesterase
Alzheimer's disease
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Abstract Diagnosis 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. N-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. Retention of the BChE radiotracer was consistently higher in the 5XFAD mouse than in WT, and differences were particularly evident in the cerebral cortex. Cerebral cortical BChE imaging with SPECT can distinguish 5XFAD mouse model from the WT counterpart.
AbstractList Abstract Introduction Diagnosis 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. Methods N ‐methylpiperidin‐4‐yl 4‐[ 123 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.
INTRODUCTIONDiagnosis 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.
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. -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. Retention of the BChE radiotracer was consistently higher in the 5XFAD mouse than in WT, and differences were particularly evident in the cerebral cortex. Cerebral cortical BChE imaging with SPECT can distinguish 5XFAD mouse model from the WT counterpart.
Introduction Diagnosis 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. Methods N‐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. 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.
Diagnosis 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. N-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. Retention of the BChE radiotracer was consistently higher in the 5XFAD mouse than in WT, and differences were particularly evident in the cerebral cortex. Cerebral cortical BChE imaging with SPECT can distinguish 5XFAD mouse model from the WT counterpart.
Author Pottie, Ian R.
Martin, Earl
Reid, George A.
DeBay, Drew R.
Darvesh, Sultan
Bowen, Chris V.
AuthorAffiliation c Department of Chemistry and Physics, Mount Saint Vincent University, Halifax, Nova Scotia, Canada
f Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
a Department of Medical Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada
d Department of Chemistry, Saint Mary's University, Halifax, Nova Scotia, Canada
b Biomedical Translational Imaging Centre, Halifax, Nova Scotia, Canada
e Department of Radiology, Dalhousie University, Halifax, Nova Scotia, Canada
AuthorAffiliation_xml – name: b Biomedical Translational Imaging Centre, Halifax, Nova Scotia, Canada
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– name: a Department of Medical Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada
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Issue 2
Keywords Molecular imaging
Neuroimaging
Alzheimer mouse model with 5 familial mutations
Single-photon emission computed tomography
123Iodine
Butyrylcholinesterase
Acetylcholinesterase
Alzheimer's disease
Language English
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Snippet Diagnosis 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...
Introduction Diagnosis of Alzheimer's disease (AD) in vivo, by molecular imaging of amyloid or tau, is constrained because similar changes can be found in...
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...
Abstract Introduction Diagnosis of Alzheimer's disease (AD) in vivo , by molecular imaging of amyloid or tau, is constrained because similar changes can be...
INTRODUCTIONDiagnosis of Alzheimer's disease (AD) in vivo, by molecular imaging of amyloid or tau, is constrained because similar changes can be found in...
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StartPage 166
SubjectTerms 123Iodine
Acetylcholinesterase
Alzheimer mouse model with 5 familial mutations
Alzheimer's disease
Butyrylcholinesterase
Molecular imaging
Neuroimaging
Single-photon emission computed tomography
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Title Targeting butyrylcholinesterase for preclinical single photon emission computed tomography (SPECT) imaging of Alzheimer's disease
URI https://dx.doi.org/10.1016/j.trci.2017.01.005
https://onlinelibrary.wiley.com/doi/abs/10.1016%2Fj.trci.2017.01.005
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