title: Increased apolipoprotein D dimer formation in Alzheimer's disease hippocampus is associated with lipid conjugated diene levels.
abstract: 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-β 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.
authors: Neuroscience Research Australia, Randwick, NSW, Australia.
authors: Surabhi
authors: S
authors: Bhatia
authors: Andrew M
authors: AM
authors: Jenner
authors: Hongyun
authors: H
authors: Li
authors: Kalani
authors: K
authors: Ruberu
authors: Adena S
authors: AS
authors: Spiro
authors: Claire E
authors: CE
authors: Shepherd
authors: Jillian J
authors: JJ
authors: Kril
authors: Nupur
authors: N
authors: Kain
authors: Anthony
authors: A
authors: Don
authors: Brett
authors: B
authors: Garner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000975:Antioxidants / Q000378:metabolism*; D053399:Apolipoproteins D / Q000378:metabolism*; D002531:Cerebellum / Q000473:pathology; D019281:Dimerization; D018450:Disease Progression; D005260:Female; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D015227:Lipid Peroxidation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism
chemical_list: C024328:APOD protein, human; D016229:Amyloid beta-Peptides; D000975:Antioxidants; D053399:Apolipoproteins D; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)