title: Cerebral Apolipoprotein-D Is Hypoglycosylated Compared to Peripheral Tissues and Is Variably Expressed in Mouse and Human Brain Regions.
abstract: Recent studies have shown that cerebral apoD levels increase with age and in Alzheimer's disease (AD). In addition, loss of cerebral apoD in the mouse increases sensitivity to lipid peroxidation and accelerates AD pathology. Very little data are available, however, regarding the expression of apoD protein levels in different brain regions. This is important as both brain lipid peroxidation and neurodegeneration occur in a region-specific manner. Here we addressed this using western blotting of seven different regions (olfactory bulb, hippocampus, frontal cortex, striatum, cerebellum, thalamus and brain stem) of the mouse brain. Our data indicate that compared to most brain regions, the hippocampus is deficient in apoD. In comparison to other major organs and tissues (liver, spleen, kidney, adrenal gland, heart and skeletal muscle), brain apoD was approximately 10-fold higher (corrected for total protein levels). Our analysis also revealed that brain apoD was present at a lower apparent molecular weight than tissue and plasma apoD. Utilising peptide N-glycosidase-F and neuraminidase to remove N-glycans and sialic acids, respectively, we found that N-glycan composition (but not sialylation alone) were responsible for this reduction in molecular weight. We extended the studies to an analysis of human brain regions (hippocampus, frontal cortex, temporal cortex and cerebellum) where we found that the hippocampus had the lowest levels of apoD. We also confirmed that human brain apoD was present at a lower molecular weight than in plasma. In conclusion, we demonstrate apoD protein levels are variable across different brain regions, that apoD levels are much higher in the brain compared to other tissues and organs, and that cerebral apoD has a lower molecular weight than peripheral apoD; a phenomenon that is due to the N-glycan content of the protein.
authors.affiliation: Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW 2522, Australia.|School of Biological Sciences, University of Wollongong, Wollongong, NSW 2522, Australia.
authors.forename: Hongyun
authors.initials: H
authors.lastname: Li
authors.affiliation: Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW 2522, Australia.|School of Biological Sciences, University of Wollongong, Wollongong, NSW 2522, Australia.
authors.forename: Kalani
authors.initials: K
authors.lastname: Ruberu
authors.affiliation: Neuroscience Research Australia, Randwick, NSW 2031, Australia.|School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia.|Schizophrenia Research Institute, Randwick, NSW 2031, Australia.
authors.forename: Tim
authors.initials: T
authors.lastname: Karl
authors.affiliation: Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW 2522, Australia.|School of Biological Sciences, University of Wollongong, Wollongong, NSW 2522, Australia.
authors.forename: Brett
authors.initials: B
authors.lastname: Garner
mesh_terms: D000818:Animals; D053399:Apolipoproteins D / Q000378:metabolism*; D001057:Apolipoproteins E / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D054022:Cerebrum / Q000378:metabolism*; D005260:Female; D006031:Glycosylation; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D008970:Molecular Weight; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D011134:Polysaccharides / Q000378:metabolism
chemical_list: D053399:Apolipoproteins D; D001057:Apolipoproteins E; D015415:Biomarkers; D011134:Polysaccharides; D019158:N-Acetylneuraminic Acid
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