Alteration of Aβ metabolism-related molecules in predementia induced by AlCl3 and D-galactose

Age (Dordr). 2009 Dec;31(4):277-84. doi: 10.1007/s11357-009-9099-y.

Abstract

The purpose of this study was to look for alterations in β-amyloid peptide (Aβ) metabolism-related molecules in predementia, the early stage of Alzheimer’s disease (AD). AlCl3 (Al) and d-galactose (D-gal) were used to induce the mouse model for predementia and AD. Protein expression of β-amyloid (Aβ), β-secretase (BACE1), neprilysin (NEP), insulin degrading enzyme (IDE) and receptor for advanced glycation end products (RAGE) in the brain was measured. The results indicated that Al + D-gal induced an AD-like behavioral deficit at 90 days. The period from 45 to 75 days showed no significant behavioral deficit, and we tentatively define this as predementia in this model. A significant increase in BACE1 and decreasing NEP characterized days 45–90 in the cortex and hippocampus. However, high Aβ occurred at day 60. IDE increased from day 60 to day 75. There was no change in RAGE. The results suggest that the observed changes in BACE1, NEP and Aβ in predementia might relate to a different stage of the AD-like pathology, which may be developed into useful biomarkers for the diagnosis of very early AD.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aluminum Chloride
  • Aluminum Compounds / pharmacology*
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / prevention & control
  • Amyloid Precursor Protein Secretases / biosynthesis
  • Amyloid beta-Peptides / biosynthesis*
  • Animals
  • Biomarkers / metabolism
  • Blotting, Western
  • Cerebral Cortex / metabolism*
  • Chlorides / pharmacology*
  • Disease Models, Animal
  • Disease Progression
  • Follow-Up Studies
  • Galactose / pharmacology*
  • Glycation End Products, Advanced / metabolism
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Insulysin / biosynthesis
  • Mice
  • Mice, Transgenic
  • Neprilysin / biosynthesis

Substances

  • Aluminum Compounds
  • Amyloid beta-Peptides
  • Biomarkers
  • Chlorides
  • Glycation End Products, Advanced
  • Aluminum Chloride
  • Amyloid Precursor Protein Secretases
  • Neprilysin
  • Insulysin
  • Galactose