Lead Exposure in Developmental Ages Promotes Aβ Accumulation by Disturbing Aβ Transportation in Blood-Cerebrospinal Fluid Barrier/Blood-Brain Barriers and Impairing Aβ Clearance in the Liver

Environmental lead exposure is closely related to the progression of Alzheimer's disease (AD). Our previous study has shown that exposure to lead could result in the cholesterol unbalance and increase amyloid-beta (A beta) generation in the brain. However, the potential effect of lead exposure on A beta transportation is poorly reported. In this study, we sought to explore whether lead exposure in developmental ages impaired the integrity of BCSFB and BBB, two highly vascularized structures in the brain in a rat model. The A beta clearance in the liver was also assessed. Our results showed that lead treatment in developmental ages increased the number of TUNEL-positive apoptotic cells in rat choroid plexus and microvessels. Moreover, lead exposure markedly increased pro-inflammatory factors expression including TNF-alpha and IL-1 beta in rat choroid plexus and microvessels. Interestingly, lead treatment increased the expression of AQP-1 and reduced the expression of TTR, two key proteins associated with the functions of choroid plexus and microvessels. Additionally, the expressions of ABCB1, LRP-1, and RAGE, three major receptors responsible for A beta transportation, were disturbed by developmental lead exposure. All these pathologies resulted in A beta(1-40) deposition within BCSFB and BBB and malfunctions of these two vascularized structures. Finally, we found that lead treatment remarkably inhibited the gene expression of LRP-1, which is responsible for A beta endocytosis, in the liver tissue of the rat model. Collectively, our results provide the first evidence that developmental lead exposure induces A beta deposition in BCSFB and BBB and impairs A beta clearance in the liver, which would ultimately disturb A beta transportation via choroid plexus/brain microvessels and facilitate A beta deposition in the brain.

Automated summary

The study showed that developmental lead exposure increased cell apoptosis in rat choroid plexus and microvessels, upregulated pro-inflammatory factors, and disrupted the expression of key proteins, affecting Aβ transportation. These pathological changes resulted in Aβ deposition within BCSFB and BBB, leading to dysfunction of these vascularized structures.