Brains of Alzheimer disease patients in early stages of dementia contain an increased 24(S)-hydroxycholesterol (cerebrosterol)/cholesterol ratio when compared to controls. In this study, effects of amyloid beta peptides and of racemic 24-hydroxycholesterol were evaluated in vitro on undepleted or cholesterol-depleted hippocampal synaptosomes of young and old rats via a high-affinity choline transport and membrane anisotropy measurements. Depletion of membrane cholesterol decreased the transport of [3H]choline, increased the specific binding of [3H]hemicholinium-3 and decreased membrane anisotropy. However, less alterations were found in old when compared to young brains. 500 nM nonaggregated peptides were ineffective but aggregated fragment 1-42 evoked marked drops in the transport and anisotropy values on depleted synaptosomes. 50 microM 24-hydroxycholesterol inhibited choline transport on depleted synaptosomes but it did not influence membrane anisotropy. Peptides eliminated the actions of oxysterol on choline carriers in young but not in old rats. On the other hand, oxysterol eliminated the effects of peptides on membrane anisotropy. Our study suggests a possible role of membrane cholesterol in the regulation of choline carriers and supports data reporting a protective role of membrane cholesterol against toxic effects of amyloid beta peptides. Moreover, via Raman spectroscopy we demonstrate for the first time that peptides form a complex with 24-hydroxycholesterol.

Alzheimer Disease Centre Prague Psychiatric Centre Ustavní 91 Prague 8 Bohnice 181 03 Czech Republic

Zobrazit více v PubMed

J Clin Invest. 2002 Sep;110(6):725-30 PubMed

Biochemistry. 2001 Jul 24;40(29):8563-71 PubMed

J Neurochem. 2003 Oct;87(1):136-46 PubMed

J Psychiatr Res. 2002 Jan-Feb;36(1):27-32 PubMed

Trends Neurosci. 2004 Jan;27(1):1-3 PubMed

J Pharmacol Exp Ther. 2004 Aug;310(2):536-45 PubMed

Biochemistry. 1975 Nov 4;14(22):4870-6 PubMed

Mol Psychiatry. 2002;7(8):899-902 PubMed

J Lipid Res. 2003 Nov;44(11):2019-29 PubMed

Neurobiol Aging. 2002 Sep-Oct;23(5):685-94 PubMed

J Am Chem Soc. 2006 Oct 18;128(41):13451-62 PubMed

FASEB J. 2002 Oct;16(12):1526-36 PubMed

J Neurosci. 2002 Mar 1;22(5):1709-17 PubMed

J Biol Chem. 1983 Jan 25;258(2):1242-53 PubMed

Biochemistry. 2000 Aug 22;39(33):10309-18 PubMed

Steroids. 2004 Jan;69(1):1-16 PubMed

J Lipid Res. 2000 Feb;41(2):195-8 PubMed

Neurobiol Aging. 2004 Sep;25(8):977-89 PubMed

Neurochem Res. 2006 Mar;31(3):351-60 PubMed

Science. 2002 May 31;296(5573):1636-9 PubMed

Brain Res. 1999 Feb 6;818(1):171-5 PubMed

J Neurochem. 1998 May;70(5):2179-87 PubMed

Subcell Biochem. 1995;24:55-99 PubMed

Neurosci Lett. 2002 May 10;324(1):83-5 PubMed

J Cell Biol. 2004 Dec 6;167(5):953-60 PubMed

Pharmacol Ther. 2001 Oct;92(1):21-55 PubMed

Proc Natl Acad Sci U S A. 1998 May 26;95(11):6460-4 PubMed

Arch Gerontol Geriatr. 1993 Nov-Dec;17(3):179-88 PubMed

Biochemistry. 1997 Sep 9;36(36):10959-74 PubMed

Biochem Soc Trans. 2001 Aug;29(Pt 4):617-23 PubMed

Neurochem Res. 2001 Mar;26(3):203-12 PubMed

J Neurochem. 1988 Apr;50(4):1309-18 PubMed

Neurosci Lett. 2000 Oct 27;293(2):87-90 PubMed

Anal Biochem. 1976 May 7;72:248-54 PubMed

J Mol Biol. 2002 Apr 19;318(1):97-107 PubMed

J Neurochem. 1990 May;54(5):1500-8 PubMed

J Biol Chem. 2001 Oct 5;276(40):37004-10 PubMed

J Neurochem. 2005 Dec;95(6):1667-76 PubMed

J Neurochem. 2002 Dec;83(5):1110-9 PubMed

Anal Chem. 2003 Nov 1;75(21):5703-9 PubMed

J Lipid Res. 2001 Aug;42(8):1292-7 PubMed

Protein τ-mediated effects on rat hippocampal choline transporters CHT1 and τ-amyloid β interactions

Interactions of amyloid β peptide 1-40 and cerebrosterol