Effect of Cerebral Amyloid Angiopathy on Brain Iron, Copper, and Zinc in Alzheimer's Disease

被引:89
作者
Schrag, Matthew [1 ]
Crofton, Andrew [1 ]
Zabel, Matthew [1 ]
Jiffry, Arshad [1 ]
Kirsch, David [1 ]
Dickson, April [1 ]
Mao, Xiao Wen [2 ]
Vinters, Harry V. [3 ,4 ]
Domaille, Dylan W. [5 ,6 ]
Chang, Christopher J. [5 ,6 ]
Kirsch, Wolff [1 ]
机构
[1] Loma Linda Univ, Neurosurg Ctr Res Training & Educ, Loma Linda, CA 92350 USA
[2] Loma Linda Univ, Mol Radiat Biol Labs, Loma Linda, CA 92350 USA
[3] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med Neuropathol, Los Angeles, CA 90095 USA
[4] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA
[5] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA
[6] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA
基金
美国国家卫生研究院;
关键词
Atomic absorption; coppersensor 1 (CS1); ferrous; non-heme iron; NEUTRON-ACTIVATION ANALYSIS; TRACE-ELEMENT CONCENTRATIONS; NON-HAEMIN IRON; OXIDATIVE STRESS; SENILE PLAQUES; TRANSFERRIN RECEPTORS; BILIVERDIN REDUCTASE; REGULATORY PROTEINS; PARKINSONS-DISEASE; FLUORESCENT SENSOR;
D O I
10.3233/JAD-2010-101503
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Cerebral amyloid angiopathy (CAA) is a vascular lesion associated with Alzheimer's disease (AD) present in up to 95% of AD patients and produces MRI-detectable microbleeds in many of these patients. It is possible that CAA-related microbleeding is a source of pathological iron in the AD brain. Because the homeostasis of copper, iron, and zinc are so intimately linked, we determined whether CAA contributes to changes in the brain levels of these metals. We obtained brain tissue from AD patients with severe CAA to compare to AD patients without evidence of vascular amyloid-beta. Patients with severe CAA had significantly higher non-heme iron levels. Histologically, iron was deposited in the walls of large CAA-affected vessels. Zinc levels were significantly elevated in grey matter in both the CAA and non-CAA AD tissue, but no vascular staining was noted in CAA cases. Copper levels were decreased in both CAA and non-CAA AD tissues and copper was found to be prominently deposited on the vasculature in CAA. Together, these findings demonstrate that CAA is a significant variable affecting transition metals in AD.
引用
收藏
页码:137 / 149
页数:13
相关论文
共 69 条
[31]   Serial Susceptibility Weighted MRI Measures Brain Iron and Microbleeds in Dementia [J].
Kirsch, Wolff ;
McAuley, Grant ;
Holshouser, Barbara ;
Petersen, Floyd ;
Ayaz, Muhammad ;
Vinters, Harry V. ;
Dickson, Cindy ;
Haacke, E. Mark ;
Britt, William, III ;
Larsen, James ;
Kim, Ivan ;
Mueller, Claudius ;
Schrag, Matthew ;
Kido, Daniel .
JOURNAL OF ALZHEIMERS DISEASE, 2009, 17 (03) :599-609
[32]   Safety, efficacy, and biomarker findings of PBT2 in targeting Aβ as a modifying therapy for Alzheimer's disease: a phase IIa, double-blind, randomised, placebo-controlled trial (vol 7, pg 779, 2008) [J].
Lannfelt, L. ;
Blennow, K. ;
Zetterberg, H. .
LANCET NEUROLOGY, 2009, 8 (11) :981-981
[33]   The family of iron responsive RNA structures regulated by changes in cellular iron and oxygen [J].
Leipuviene, R. ;
Theil, E. C. .
CELLULAR AND MOLECULAR LIFE SCIENCES, 2007, 64 (22) :2945-2955
[34]   Human biliverdin reductase: A member of the insulin receptor substrate family with serine/threonine/tyrosine kinase activity [J].
Lerner-Marmarosh, N ;
Shen, J ;
Torno, MD ;
Kravets, A ;
Hu, ZB ;
Maines, MD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (20) :7109-7114
[35]  
LOEFFLER DA, 1995, J NEUROCHEM, V65, P710
[36]   Copper, iron and zinc in Alzheimer's disease senile plaques [J].
Lovell, MA ;
Robertson, JD ;
Teesdale, WJ ;
Campbell, JL ;
Markesbery, WR .
JOURNAL OF THE NEUROLOGICAL SCIENCES, 1998, 158 (01) :47-52
[37]   Iron, copper, and iron regulatory protein 2 in Alzheimer's disease and related dementias [J].
Magaki, Shino ;
Raghavan, Ravi ;
Mueller, Claudius ;
Oberg, Kerby C. ;
Vinters, Harry V. ;
Kirsch, Wolff M. .
NEUROSCIENCE LETTERS, 2007, 418 (01) :72-76
[38]   The role of oxidative stress in Alzheimer disease [J].
Markesbery, WR .
ARCHIVES OF NEUROLOGY, 1999, 56 (12) :1449-1452
[39]   BRAIN TRACE-ELEMENT CONCENTRATIONS IN AGING [J].
MARKESBERY, WR ;
EHMANN, WD ;
ALAUDDIN, M ;
HOSSAIN, TIM .
NEUROBIOLOGY OF AGING, 1984, 5 (01) :19-28
[40]   INTRAMUSCULAR DESFERRIOXAMINE IN PATIENTS WITH ALZHEIMERS-DISEASE [J].
MCLACHLAN, DRC ;
DALTON, AJ ;
KRUCK, TPA ;
BELL, MY ;
SMITH, WL ;
KALOW, W ;
ANDREWS, DF .
LANCET, 1991, 337 (8753) :1304-1308