Selective accumulation of aluminum in cerebral arteries in Alzheimer's disease (AD)

被引:48
作者
Bhattacharjee, Surjyadipta [1 ]
Zhao, Yuhai [1 ]
Hill, James M. [1 ,2 ]
Culicchia, Frank [1 ,3 ]
Kruck, Theodore P. A. [4 ,5 ]
Percy, Maire E. [4 ,5 ]
Pogue, Aileen I. [6 ]
Walton, J. R. [7 ]
Lukiw, Walter J. [1 ,2 ]
机构
[1] Louisiana State Univ, Hlth Sci Ctr, Ctr Neurosci, New Orleans, LA 70112 USA
[2] Louisiana State Univ, Hlth Sci Ctr, Dept Neurol & Ophthalmol, New Orleans, LA 70112 USA
[3] Louisiana State Univ, Hlth Sci Ctr, Dept Neurosurg, New Orleans, LA 70112 USA
[4] Univ Toronto, Neurogenet Lab, Surrey Pl Ctr, Toronto, ON M5S 1A8, Canada
[5] Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, Canada
[6] Alchem Biotech, Toronto, ON M5S 1A8, Canada
[7] Univ New S Wales, Sydney, NSW 2204, Australia
关键词
Aluminum sulfate; Alzheimer's disease; Endothelial cells; Genotoxicity; Human brain microvessel endothelial cells; Inflammation; NF-KAPPA-B; CELLS; EXPRESSION; COPPER; ROS;
D O I
10.1016/j.jinorgbio.2013.05.007
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Once biologically available aluminum bypasses gastrointestinal and blood-brain barriers, this environmentally-abundant neurotoxin has an exceedingly high affinity for the large pyramidal neurons of the human brain hippocampus. This same anatomical region of the brain is also targeted by the earliest evidence of Alzheimer's disease (AD) neuropathology. The mechanism for the selective targeting and transport of aluminum into the hippocampus of the human brain is not well understood. In an effort to improve our understanding of a pathological aluminum entry system into the brain, this study examined the aluminum content of 8 arteries that supply blood to the hippocampus, including the aorta and several cerebral arteries. In contrast to age-matched controls, in AD patients we found a gradient of increasing aluminum concentration from the aorta to the posterior cerebral artery that supplies blood to the hippocampus. Primary cultures of human brain endothelial cells were found to have an extremely high affinity for aluminum when compared to other types of brain cells. Together, these results suggest for the first time that endothelial cells that line the cerebral vasculature may have biochemical attributes conducive to binding and targeting aluminum to selective anatomical regions of the brain, such as the hippocampus, with potential downstream pro-inflammatory and pathogenic consequences. (C) 2013 Elsevier Inc. All rights reserved.
引用
收藏
页码:35 / 37
页数:3
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