Amyloid Efflux Transporter Expression at the Blood-Brain Barrier Declines in Normal Aging

作者：Silverberg Gerald D^*; Messier Arthur A; Miller Miles C; Machan Jason T; Majmudar Samir S; Stopa Edward G; Donahue John E; Johanson Conrad E

来源：Journal of Neuropathology and Experimental Neurology, 2010, 69(10): 1034-1043.

DOI：10.1097/NEN.0b013e3181f46e25

• Aging
• Alzheimer disease
• Amyloid
• Blood-brain barrier
• LRP-1
• P-gp
• RAGE

Reduced clearance of amyloid beta peptides (A beta) across the blood-brain barrier contributes to amyloid accumulation in Alzheimer disease. Amyloid beta efflux transport is via the endothelial low-density lipoprotein receptor-related protein 1 (LRP-1) and P-glycoprotein (P-gp), whereas A beta influx transport is via the receptor for advanced glycation end products. Because age is the major risk factor for developing Alzheimer disease, we measured LRP-1 and P-gp expression and associated transporter expression with A beta accumulation in aging rats. Quantitative LRP-1 and P-gp microvessel expression was measured by immunohistochemistry (IHC); LRP-1 and P-gp expression were assessed in microvessel isolates by Western blotting. There was an age-dependent loss of capillary LRP-1 across all ages (3-36 months) by IHC (linear trend p = 0.0004) and between 3 and 20 months by Western blotting (linear trend p < 0.0001). There was a late (30-36 months) P-gp expression loss by IHC (p < 0.05) and Western blotting (p = 0.0112). Loss of LRP-1 correlated with A beta 42 accumulation (p = 0.0121) and very nearly with A beta 40 (p = 0.0599) across all ages. Expression of LRP-1 correlated negatively with the expression of receptor for advanced glycation end products (p G 0.0004). These data indicate that alterations in LRP-1 and P-gp expression seem to contribute progressively to A beta accumulation in aging.

• 出版日期2010-10