Amyloid beta deposition is related to decreased glucose transporter-1 levels and hippocampal atrophy in brains of aged APP/PS1 mice.

Carlijn R Hooijmans, Coen Graven, Pieter J Dederen, Heikki Tanila, Thomas van Groen, Amanda J Kiliaan

Radboud University Nijmegen Medical Centre, Department of Anatomy, Geert Grooteplein noord 21 6500 HB Nijmegen, The Netherlands.

Brain research 2007 Nov 21

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The amount of the glucose transporter type-1 (GLUT-1) is decreased in the hippocampus and cerebral cortex of AD patients. In this study we therefore wanted to investigate the causal relationship between beta-amyloid (Abeta), GLUT-1 and hippocampal atrophy in the brains of young (8 months) and old (18 months) APP/PS1 mice. Abeta and GLUT-1 were visualized immunohistochemically. Abeta load, GLUT-1 amount, capillary density and GLUT-1 amount per capillary density were determined in cortical and hippocampal areas using computer-assisted analysis systems. Hippocampal atrophy was determined by calculating the width of the outer molecular layer of the dentate gyrus (DG). In 18-month-old APP/PS1 mice we found a reduced GLUT-1 amount in the hippocampus but no differences in capillary density. The DG of these mice contained the highest level of Abeta in combination with hippocampal atrophy, and a reduced GLUT-1 amount per capillary density. At 8 months, no differences were observed. The highest Abeta deposition was found in the DG, although fourfold less compared to 18-month-old mice. We conclude that the GLUT-1 amount and capillary density in both wild type and transgenic mice decrease due to ageing. Further, a decreased amount of GLUT-1 is caused by decreased GLUT-1 amount/capillary density and not due to a reduced capillary density. We suggest that Abeta load in the hippocampus precedes the reduction of GLUT-1. A certain level of Abeta must be reached in the hippocampus, before it affects GLUT-1 amount/capillary density leading to further impairment of energy metabolism and hippocampal atrophy.

Citation

Carlijn R Hooijmans, Coen Graven, Pieter J Dederen, Heikki Tanila, Thomas van Groen, Amanda J Kiliaan. Amyloid beta deposition is related to decreased glucose transporter-1 levels and hippocampal atrophy in brains of aged APP/PS1 mice. Brain research. 2007 Nov 21;1181:93-103