Scavenger receptor class B type I expression and elemental analysis in cerebellum and parietal cortex regions of the Alzheimer's disease brain.
Metal ions play an important role in health and disease by influencing cellular biochemical pathways. The increased concentrations of some metal ions may have cytotoxic effects through their ability to oxidatively modify biomolecules, which may cause oxidative stress-induced brain cell death leading to neurodegenerative disorders observed in Alzheimer's disease (AD). We therefore performed elemental analysis of human brain tissues by a sophisticated method of inductively coupled plasma mass spectrometry (ICP-MS) in two regions of the AD brain, the parietal cortex and cerebellum, and compared them with the age-matched control. Our analysis shows the differential distribution of some metal ions in the two regions of the brain. Most importantly, Si, Sn, Al and Mn showed significantly higher levels in the parietal cortex of the AD brain compared to the control. The other metal ions showing moderate increases in the parietal cortex were Na, Te, Cr, Fe and B. Since these metal ions can modify lipoproteins in the brain and modified lipoproteins are taken up by scavenger receptors class B type I (SR-BI), we also determined the presence of SR-BI in the parietal cortex and cerebellum regions of the control and AD brains using a sensitive method, the reverse transcriptase-polymerase chain reaction. Our results suggest that SR-BI are present in the parietal cortex as well as in the cerebellum of the control and AD brains, suggesting that the presence of SR-BI may be involved in the uptake of oxidatively modified lipoproteins and beta-amyloid (Abeta) protein complexed with apoE, suggesting implications in the progression of late onset AD and other neurodegenerative disorders characterized by the deposition of insoluble aggregates observed in the AD brain.
Srivastava
Rai Ajit K
RA
Washington University School of Medicine, Saint Louis, MO 63110, USA. ajits@esperion.com
Jain
Jinesh C
JC
D000368:Aged; D000369:Aged, 80 and over; D000535:Aluminum / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D018955:CD36 Antigens / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006801:Humans; D007477:Ions / Q000378:metabolism*; D008074:Lipoproteins / Q000378:metabolism; D008345:Manganese / Q000378:metabolism; D008565:Membrane Proteins; D008670:Metals / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D010296:Parietal Lobe / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D012825:Silicon / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
D018955:CD36 Antigens; D007477:Ions; D008074:Lipoproteins; D008565:Membrane Proteins; D008670:Metals; D017382:Reactive Oxygen Species; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C495124:SCARB1 protein, human; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D008345:Manganese; D000535:Aluminum; D013482:Superoxide Dismutase; D012825:Silicon