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

Brain Res. 2007 Nov 21;1181:93-103. doi: 10.1016/j.brainres.2007.08.063. Epub 2007 Sep 5.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism
  • Aging / pathology
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism
  • Analysis of Variance
  • Animals
  • Atrophy
  • Capillaries / physiology*
  • Energy Metabolism / physiology*
  • Glucose Transporter Type 1 / metabolism*
  • Hippocampus / blood supply
  • Hippocampus / metabolism
  • Hippocampus / pathology*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Statistics, Nonparametric

Substances

  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Glucose Transporter Type 1