Downregulation of LPR1 at the blood–brain barrier in streptozotocin-induced diabetic mice

Deposition of amyloid-β peptide (Aβ) in the diabetic brain is poorly understood. Low-density lipoprotein receptor related protein 1(LRP1) at the blood–brain barrier (BBB) is critical for regulation of Aβ homeostasis in the brain. In this study, we used streptozotocin-induced diabetic mice to observe the expression of LRP1 at the BBB by Western blot and immunocytochemical analysis, and to study in vivo brain-to-blood efflux transport of 125I-Aβ1–40 using brain clearance studies. In the diabetic mice with hyperglycemia (>16.0mmol/l) at 6weeks, LRP1 expression at the BBB was significantly downregulated; no significant changes of LRP1 levels were found at 1 and 3weeks after diabetes induction. The data of brain clearance studies for Aβ showed significant decrease in LRP1-dependent transport of Aβ across the BBB at 6weeks after diabetes induction, while no significant changes of LRP1-dependent transport of Aβ across the BBB at 1 or 3weeks after diabetes induction were apparent. We conclude that the downregulation of LRP1 at the BBB contributes to cerebral Aβ deposition in diabetes mellitus.