Altered expression of Aβ metabolism-associated molecules from d-galactose/AlCl3 induced mouse brain

Cerebral deposition of amyloid-β peptide (Aβ) is a critical feature of Alzheimer's disease (AD). Either aluminium trichloride (Al) or d-galactose (d-gal) induces Aβ overproduction in rat or mouse brain and has been used to produce models of aging and AD. Here it is shown that mice treated with Al plus d-gal represent a good model of AD with altered expression of Aβ metabolism-associated molecules. The work shows that Al/d-gal causes memory impairment and high Aβ levels in the cortex (Co) and hippocampus (Hi). Then, we found that beta-site APP cleavage enzyme 1 (BACE1) was increased in mouse Co and Hi. Al or Al plus d-gal suppressed mRNA of the low-density lipoprotein receptor-related protein 1(LRP1). d-gal also decreased the LRP expression in Hi, but not in Co. However, Al/d-gal did not affect the receptor for advanced glycation end products (RAGE) expression in mouse brains. Furthermore, Al/d-gal reduced the expression of neprilysin (NEP), but not the insulin degrading enzyme (IDE). This study indicates that Al/d-gal affects the expression of Aβ metabolism-associated molecules that are responsible for Aβ deposition during AD, suggesting that this mouse model can be a useful model for studying the mechanisms and biomarkers of AD and for drug screening.