The pathological role of Pb in AD through impairing functions of blood‐brain barrier system

Abstract Background Lead (Pb) is an environmental factor has been suspected of contributing to Alzheimer’s disease (AD) and other dementia. Our previous study has shown that chronic Pb exposure increased brain levels of beta‐amyloid (Aβ) and amyloid plaques, a pathological hallmark for AD, in APP transgenic mice possibly by inhibiting Aβ clearance. However, it remains unclear how different levels of Pb affect Aβ clearance and the blood‐brain system (BBBS) in the blood‐brain barrier system. Method Tg‐APP mice were administrated with Pb‐acetate at three different doses by oral gavage for 4 weeks. Dynamic contrast‐enhanced CT (DCE‐CT) imaging method was used to quantify the real‐time brain regional blood flow, blood volume, and BBBS permeability. Result Chronic Pb exposures significantly increased permeability surface area product (PS) and brain perfusion, indicating that Pb disrupted the mouse blood‐brain barrier system was possibly mediated by inflammation. Conclusion Chronic Pb exposure at toxic and even subtoxic levels would damage the BBBS and induce dementia by allowing blood contents to escape into the brain parenchyma.