Naslov
The role of lipid rafts on app processing and Amyloid-β formation

Autori
Košiček, Marko ; Goate, Alison ; Katušić Hećimović, Silva

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
4. hrvatski kongres o Alzheimerovoj bolesti s međunarodnim sudjelovanjem : knjiga sažetaka ; u: Neurologia Croatica 57 (2008) (S4) / - , 2008, 70-70

Skup
Hrvatski kongres o Alzheimerovoj bolesti s međunarodnim sudjelovanjem (4 ; 2008)

Mjesto i datum
Rovinj, Hrvatska, 08.10.2008. - 11.10.2008

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
Alzheimer's disease; cholesterol; APP protein; Abeta peptide; lipid rafts

Sažetak
Retrospective epidemiological studies have recently shown that cholesterol-lowering drugs (statins) may decrease the prevalence of Alzheimer disease (AD) and that hypercholesterolemia may be a risk factor for AD. It has been also observed that cholesterol accumulation in lysosomal storage disorder Niemann Pick type C (NPC) leads to increase Aβ , like in AD. In addition, lipid rafts, a cholesterol and sphingolipid rich membrane microdomains, have been found as a site of Aβ formation. Since cholesterol levels have shown to modulate APP processing and Aβ production, both in vitro and in vivo, we hypothesized that cholesterol-effect on Aβ may be mediated through lipid rafts. To test this we monitored APP localization and Aβ formation in lipid rafts between CHO NPC1-null (M12) and CHOwt cells by the two methods: lipid raft isolation and confocal microscopy. We showed that M12 cells exert an NPC-like phenotype: they have increased levels of cholesterol, increased C99/CTFβ and increased Aβ levels compared to CHOwt cells. Lipid rafts were isolated using zwitterionic (CHAPSO) or nonionic (Triton X-100, Lubrol-WX) detergent in a discontinuous sucrose gradient. By western blotting we show that only a minor fraction of APP and Aβ were localized in lipid rafts in both CHOwt and CHO NPC1-null cells. In addition, we did not observe altered lipid raft compartmentalization of APP between CHOwt and M12 cells. Using confocal microscopy we confirmed that in CHO cells less APP and Aβ are found in lipid rafts, suggesting that lipid rafts may not be a primary site of APP processing. In addition, we did not observe any substantial difference between APP and lipid raft, as well as Aβ and lipid raft colocalization between CHOwt and CHO NPC1-null cells. In summary, our results show that increased formation of Aβ upon cholesterol accumulation in NPC1-deficient CHO cells does not involve lipid rafts, suggesting that the mechanism of cholesterol-effect on Aβ may not be mediated through these cholesterol and sphingolipid rich membrane microdomains.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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