THE LEVELS OF SOLUBLE AMYLOID b PROTEIN IN DIFFERENT HDL FRACTIONS DISTINGUISH ALZHEIMER'S AND NORMAL AGING CSF

N.V. Koudinova^1,2; T.T. Berezov ¹; A.A. Boldyrev^1*; A.R. Koudinov^1,2

1. Russian Acad Med Sci, Nat Mental Health Res Ctr, Inst Biomed Chem, Lab Clin Neurochem, Timoshenko 38-27, Moscow 121359, Russian Federation

2. Neurobiol and Biol Regulation, Weizmann Institute, Rehovot 76100, Israel

We and others previously reported that in both normal human plasma and CSF soluble form of Alzheimer's (AD) amyloid beta protein (sAb) is associated with high density lipoprotein particles (HDL). The aim of the present study was to elucidate the AD specific pattern of sAb distribution in CSF HDL. AD and normal human CSF HDL were fractionated and analyzed essentially as we described previously (BBRC 1996;223:592;   Soc Neurosci Abst 1998;24:723). In contrast to normal human, AD CSF had different apolipoprotein (apo) distribution among different HDL species. Normal human CSF HDL of 1.063 g/ml floating density (HDL1) was quantitatively minor (in comparison to a denser HDL2, HDL3 and very high density (VHDL) lipoprotein). Contrarily, AD CSF-HDL1 had significant apolipoprotein load, mainly apoE and apoA1. The most intriguing was preferred partitioning of Ab into the AD CSF-HDL1, in contrast to normal CSF, where the peptide was preferentially distributed in HDL3 and VHDL. Moreover, AD CSF HDL2 and HDL3+VHDL tended to have sAb associated with apoE and apoJ, not observed in AD CSF HDL3 and VHDL and in normal CSF-HDL even under the intraparticle crosslinkage (Soc Neurosci Abst  1997;23:537). Our observation may i) be of great importance in distinguishing AD cases from normal aging by assessing sAb and (apo)lipoprotein distribution in CSF HDL, and ii) revitalize the discussion on possible role of CNS HDL and apolipoproteins and lipids in AD an Ab pathophysiology.

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