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 (Abeta), GLUT-1 and hippocampal atrophy in the brains of young (8 months) and old (18 months) APP/PS1 mice.


METHODS
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).


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 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.


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 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.
Hooijmans
Carlijn R
CR
Radboud University Nijmegen Medical Centre, Department of Anatomy, Geert Grooteplein noord 21 6500 HB Nijmegen, The Netherlands.
Graven
Coen
C
Dederen
Pieter J
PJ
Tanila
Heikki
H
van Groen
Thomas
T
Kiliaan
Amanda J
AJ
D000375:Aging / Q000378:metabolism / Q000473:pathology; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001284:Atrophy; D002196:Capillaries / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology*; D051272:Glucose Transporter Type 1 / Q000378:metabolism*; D006624:Hippocampus / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018709:Statistics, Nonparametric
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D051272:Glucose Transporter Type 1