Increased Apolipoprotein D Dimer Formation in Alzheimer's Disease Hippocampus is Associated with Lipid Conjugated Diene Levels

被引：26

作者：

Bhatia, Surabhi ^{[1
,2
,3
]}

Jenner, Andrew M. ^{[3
,4
]}

Li, Hongyun ^{[3
,4
]}

Ruberu, Kalani ^{[3
,4
]}

Spiro, Adena S. ^{[3
,4
]}

Shepherd, Claire E. ^{[1
]}

Kril, Jillian J. ^{[5
]}

Kain, Nupur ^{[6
]}

Don, Anthony ^{[6
]}

Garner, Brett ^{[3
,4
]}

机构：

[1] Neurosci Res Australia, Randwick, NSW, Australia

[2] Univ New S Wales, Sch Med Sci, Sydney, NSW, Australia

[3] Univ Wollongong, Illawarra Hlth & Med Res Inst, Wollongong, NSW 2522, Australia

[4] Univ Wollongong, Sch Biol Sci, Wollongong, NSW 2522, Australia

[5] Univ Sydney, Disciplines Med & Pathol, Sydney, NSW 2006, Australia

[6] Univ New S Wales, Fac Med, Prince Wales Clin Sch, Sydney, NSW, Australia

来源：

JOURNAL OF ALZHEIMERS DISEASE | 2013年 / 35卷 / 03期

基金：

英国医学研究理事会; 澳大利亚研究理事会;

关键词：

Apolipoprotein D; lipid peroxidation; oxidative stress; protein dimerization; OXIDATIVE STRESS; BETA-PEPTIDE; D EXPRESSION; BRAIN; PEROXIDATION; F-2-ISOPROSTANES; DEPOSITION; RESISTANCE; HOMOLOG; CORTEX;

D O I：

10.3233/JAD-122278

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Previous studies indicate that apolipoprotein D (apoD) may have a lipid antioxidant function in the brain. We have shown that apoD can reduce free radical-generating lipid hydroperoxides to inert lipid hydroxides in a reaction that involves conversion of surface exposed apoD methione-93 (Met93) residue to Met93-sulfoxide (Met93-SO). One consequence of this reaction is the formation of a stable dimerized form of apoD. As cerebral lipid peroxidation is associated with Alzheimer's disease (AD), in the present study we aimed to assess the possible presence of apoD dimers in postmortem hippocampal and cerebellar tissues derived from a cohort of pathologically defined cases ranging from control to late stage AD. Both soluble and insoluble (requiring guanidine HCl extraction) fractions of tissue homogenates were analyzed for apoD and its dimerized form. We also assessed amyloid-beta levels by ELISA and levels of lipid peroxidation by lipid conjugated diene and F2-isoprostane analysis. Our studies reveal a significant association between soluble apoD levels and AD Braak stage whereas apoD dimer formation appears to increase predominantly in the advanced stages of disease. The formation of apoD dimers is closely correlated to lipid conjugated diene levels and occurs in the hippocampus but not in the cerebellum. These results are consistent with the hypothesis that apoD acts as a lipid antioxidant in the brain.

引用

页码：475 / 486

页数：12

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