Lead exposure induces Alzheimers's disease (AD)-like pathology and disturbes cholesterol metabolism in the young rat brain.

ABSTRACT

Lead exposure has been evidenced as a risk factor for Alzheimer's disease (AD), mainly affecting the ageing. However, the early manifestation and mechanisms of AD-like pathology induced by lead exposure remains to be elucidated. Considering the fact that impaired cholesterol metabolism is associated with many neurodegenerative disorders including AD, in this study we focused on the role of cholesterol metabolism in lead induced premature AD-like pathology. We treated weaning rats with lead at different concentrations for 4 weeks. We found that developmental lead exposure increased amyloid-beta (Aß) accumulation and amyloid plaque deposition in the cortex and hippocampus. Lead exposure increased amyloid precursor protein (APP) expression and activated the sterol regulatory element binding protein 2 (SREBP2)-beta secretase (BACE1) pathway. In addition, we found that lead exposure decreased cholesterol levels by upregulating the expression of liver X receptor-a (LXR-a) and ATP-binding cassette transporter protein family member A1 (ABCA1) and decreasing the expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CR) and low density lipoprotein receptor (LDL-R) in young rat brain tissues. Taken together, our data demonstrated that developmental lead exposure induced early manifestation of AD-like pathology and disturbed cholesterol metabolism in young rat brains.