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

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 (A beta), GLUT-1 and hippocampal atrophy in the brains of young (8 months) and old (18 months) APP/PS1 mice. Methods: A beta and GLUT-1 were visualized immunohistochemically. A beta 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). Results: In 18-month-old APP/PS1 mice we found a reduced GLUT-1 amount in the hippocampus but no differences in capillary density. The DC of these mice contained the highest level of A beta in combination with hippocampal atrophy, and a reduced GLUT-1 amount per capillary density. At 8 months, no differences were observed. The highest A beta deposition was found in the DG, although fourfold less compared to 18-month-old mice. Conclusions: 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 A beta load in the hippocampus precedes the reduction of GLUT-1. A certain level of A beta must be reached in the hippocampus, before it affects GLUT-1 amount/capillary density leading to further impairment of energy metabolism and hippocampal atrophy. (c) 2007 Elsevier B.V. All rights reserved.