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GLP-1 analog raises glucose transport capacity of blood-brain barrier in Alzheimer's disease

Publikation: Forskning - peer reviewKonferenceabstrakt i tidsskrift

M. Gejl, B. Brock, L. Egefjord, J. Rungby, A. Gjedde

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) ( 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.
TidsskriftJournal of Cerebral Blood Flow and Metabolism
Sider (fra-til)21-22
StatusUdgivet - apr. 2017

ID: 182544462