[18F] ASEM PET imaging of the alpha 7 nicotinic cholinergic receptor: test retest and sex differences

D.F. Wong; H. Kuwabara; J. Roberts; J. Brasic; C. Mishra; K. Kitzmiller; M. McDonald; L. Gapasin; A. Nandi; G. Wand; A. Gjedde; A. Horti

doi:10.1177/0271678X17695978

[¹⁸F] ASEM PET imaging of the alpha 7 nicotinic cholinergic receptor: test retest and sex differences

D.F. Wong, H. Kuwabara, J. Roberts, J. Brasic, C. Mishra, K. Kitzmiller, M. McDonald, L. Gapasin, A. Nandi, G. Wand, A. Gjedde, A. Horti

Department of Neuroscience

Abstract

Objectives: Glucose enters the brain tissue from plasma by facilitated diffusion across the two membranes of the endothelium of the blood-brain barrier (BBB), mediated by the glucose transporter 1 (GLUT1). There is evidence in Alzheimer's disease (AD) of reduction of glucose transport across the blood-brain barrier, due to diminished GLUT1 translocation and expression at the BBB. Reduced BBB GLUT1 expression is known to aggravate AD pathology and further impair cognitive function, implying that GLUT1 may be a potential target of therapy directed towards AD neurovascular dysfunction and degeneration. Hypothesis: The incretin hormone GLP-1 prevents the decline of the cerebral metabolic rate of glucose that signifies cognitive impairment, synaptic dysfunction, and disease evolution in AD, and GLP-1 may directly activate GLUT1 transport in brain capillary endothelium. For this reason, we here claim that the GLP-1 analog liraglutide may prevent the decline of blood-brain glucose transfer in AD. Methods: In this 26-week test of the hypothesis, we randomized 38 patients with AD to treatment with the GLP-1 analog liraglutide (n = 18) or placebo (n = 20). We determined blood-brain glucose transport capacity (Tmax) with [18F]FDG (FDG) (ClinicalTrials.gov NCT01469351). Results: In both groups, the Tmax estimates declined in proportion to the duration of AD. The GLP-1 analog treatment very significantly (P < 0.0001) raised the average Tmax estimate in cerebral cortex as a whole compared to the placebo treatment, from 0.72 to 1.1 mmol/hg/min. Conclusion: The results are consistent with the claim that GLP-1 analog treatment raises GLUT1 activity in the BBB and hence may represent a therapeutic target for neurovascular dysfunction and degeneration in AD.

Original language	English
Article number	BPS03-1
Journal	Journal of Cerebral Blood Flow and Metabolism
Volume	37
Issue number	1 suppl
Pages (from-to)	79
Number of pages	1
ISSN	0271-678X
DOIs	https://doi.org/10.1177/0271678X17695978
Publication status	Published - 2017

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Wong, D. F., Kuwabara, H., Roberts, J., Brasic, J., Mishra, C., Kitzmiller, K., McDonald, M., Gapasin, L., Nandi, A., Wand, G., Gjedde, A., & Horti, A. (2017). [¹⁸F] ASEM PET imaging of the alpha 7 nicotinic cholinergic receptor: test retest and sex differences. Journal of Cerebral Blood Flow and Metabolism, 37(1 suppl), 79. [BPS03-1]. https://doi.org/10.1177/0271678X17695978

Wong, DF, Kuwabara, H, Roberts, J, Brasic, J, Mishra, C, Kitzmiller, K, McDonald, M, Gapasin, L, Nandi, A, Wand, G, Gjedde, A & Horti, A 2017, '[¹⁸F] ASEM PET imaging of the alpha 7 nicotinic cholinergic receptor: test retest and sex differences', Journal of Cerebral Blood Flow and Metabolism, vol. 37, no. 1 suppl, BPS03-1, pp. 79. https://doi.org/10.1177/0271678X17695978

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title = "[18F] ASEM PET imaging of the alpha 7 nicotinic cholinergic receptor: test retest and sex differences",

abstract = "Objectives: Glucose enters the brain tissue from plasma by facilitated diffusion across the two membranes of the endothelium of the blood-brain barrier (BBB), mediated by the glucose transporter 1 (GLUT1). There is evidence in Alzheimer's disease (AD) of reduction of glucose transport across the blood-brain barrier, due to diminished GLUT1 translocation and expression at the BBB. Reduced BBB GLUT1 expression is known to aggravate AD pathology and further impair cognitive function, implying that GLUT1 may be a potential target of therapy directed towards AD neurovascular dysfunction and degeneration. Hypothesis: The incretin hormone GLP-1 prevents the decline of the cerebral metabolic rate of glucose that signifies cognitive impairment, synaptic dysfunction, and disease evolution in AD, and GLP-1 may directly activate GLUT1 transport in brain capillary endothelium. For this reason, we here claim that the GLP-1 analog liraglutide may prevent the decline of blood-brain glucose transfer in AD. Methods: In this 26-week test of the hypothesis, we randomized 38 patients with AD to treatment with the GLP-1 analog liraglutide (n = 18) or placebo (n = 20). We determined blood-brain glucose transport capacity (Tmax) with [18F]FDG (FDG) (ClinicalTrials.gov NCT01469351). Results: In both groups, the Tmax estimates declined in proportion to the duration of AD. The GLP-1 analog treatment very significantly (P < 0.0001) raised the average Tmax estimate in cerebral cortex as a whole compared to the placebo treatment, from 0.72 to 1.1 mmol/hg/min. Conclusion: The results are consistent with the claim that GLP-1 analog treatment raises GLUT1 activity in the BBB and hence may represent a therapeutic target for neurovascular dysfunction and degeneration in AD.",

author = "D.F. Wong and H. Kuwabara and J. Roberts and J. Brasic and C. Mishra and K. Kitzmiller and M. McDonald and L. Gapasin and A. Nandi and G. Wand and A. Gjedde and A. Horti",

year = "2017",

doi = "10.1177/0271678X17695978",

language = "English",

volume = "37",

pages = "79",

journal = "Journal of Cerebral Blood Flow and Metabolism",

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TY - ABST

T1 - [18F] ASEM PET imaging of the alpha 7 nicotinic cholinergic receptor

T2 - test retest and sex differences

AU - Wong, D.F.

AU - Kuwabara, H.

AU - Roberts, J.

AU - Brasic, J.

AU - Mishra, C.

AU - Kitzmiller, K.

AU - McDonald, M.

AU - Gapasin, L.

AU - Nandi, A.

AU - Wand, G.

AU - Gjedde, A.

AU - Horti, A.

PY - 2017

Y1 - 2017

N2 - Objectives: Glucose enters the brain tissue from plasma by facilitated diffusion across the two membranes of the endothelium of the blood-brain barrier (BBB), mediated by the glucose transporter 1 (GLUT1). There is evidence in Alzheimer's disease (AD) of reduction of glucose transport across the blood-brain barrier, due to diminished GLUT1 translocation and expression at the BBB. Reduced BBB GLUT1 expression is known to aggravate AD pathology and further impair cognitive function, implying that GLUT1 may be a potential target of therapy directed towards AD neurovascular dysfunction and degeneration. Hypothesis: The incretin hormone GLP-1 prevents the decline of the cerebral metabolic rate of glucose that signifies cognitive impairment, synaptic dysfunction, and disease evolution in AD, and GLP-1 may directly activate GLUT1 transport in brain capillary endothelium. For this reason, we here claim that the GLP-1 analog liraglutide may prevent the decline of blood-brain glucose transfer in AD. Methods: In this 26-week test of the hypothesis, we randomized 38 patients with AD to treatment with the GLP-1 analog liraglutide (n = 18) or placebo (n = 20). We determined blood-brain glucose transport capacity (Tmax) with [18F]FDG (FDG) (ClinicalTrials.gov NCT01469351). Results: In both groups, the Tmax estimates declined in proportion to the duration of AD. The GLP-1 analog treatment very significantly (P < 0.0001) raised the average Tmax estimate in cerebral cortex as a whole compared to the placebo treatment, from 0.72 to 1.1 mmol/hg/min. Conclusion: The results are consistent with the claim that GLP-1 analog treatment raises GLUT1 activity in the BBB and hence may represent a therapeutic target for neurovascular dysfunction and degeneration in AD.

AB - Objectives: Glucose enters the brain tissue from plasma by facilitated diffusion across the two membranes of the endothelium of the blood-brain barrier (BBB), mediated by the glucose transporter 1 (GLUT1). There is evidence in Alzheimer's disease (AD) of reduction of glucose transport across the blood-brain barrier, due to diminished GLUT1 translocation and expression at the BBB. Reduced BBB GLUT1 expression is known to aggravate AD pathology and further impair cognitive function, implying that GLUT1 may be a potential target of therapy directed towards AD neurovascular dysfunction and degeneration. Hypothesis: The incretin hormone GLP-1 prevents the decline of the cerebral metabolic rate of glucose that signifies cognitive impairment, synaptic dysfunction, and disease evolution in AD, and GLP-1 may directly activate GLUT1 transport in brain capillary endothelium. For this reason, we here claim that the GLP-1 analog liraglutide may prevent the decline of blood-brain glucose transfer in AD. Methods: In this 26-week test of the hypothesis, we randomized 38 patients with AD to treatment with the GLP-1 analog liraglutide (n = 18) or placebo (n = 20). We determined blood-brain glucose transport capacity (Tmax) with [18F]FDG (FDG) (ClinicalTrials.gov NCT01469351). Results: In both groups, the Tmax estimates declined in proportion to the duration of AD. The GLP-1 analog treatment very significantly (P < 0.0001) raised the average Tmax estimate in cerebral cortex as a whole compared to the placebo treatment, from 0.72 to 1.1 mmol/hg/min. Conclusion: The results are consistent with the claim that GLP-1 analog treatment raises GLUT1 activity in the BBB and hence may represent a therapeutic target for neurovascular dysfunction and degeneration in AD.

U2 - 10.1177/0271678X17695978

DO - 10.1177/0271678X17695978

M3 - Conference abstract in journal

SN - 0271-678X

VL - 37

SP - 79

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

IS - 1 suppl

M1 - BPS03-1

ER -

[18F] ASEM PET imaging of the alpha 7 nicotinic cholinergic receptor: test retest and sex differences

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[¹⁸F] ASEM PET imaging of the alpha 7 nicotinic cholinergic receptor: test retest and sex differences