The levels of soluble amyloid beta in different high density lipoprotein subfractions distinguish Alzheimer's and normal aging cerebrospinal fluid: implication for brain cholesterol pathology?

Several previous studies reported the association of the soluble form of am yloid beta (sA beta) protein, a major constituent of amyloid deposits in Al zheimer's disease (AD), with normal blood, cerebrospinal fluid (CSF) and ce ntral nervous system high density lipoproteins (HDLs). The present report a imed to elucidate the pattern of sA beta and apolipoprotein (apo) distribut ion in AD CSF-HDL subfractions. We studied AD CSF-HDL subfractions by SDS/P AGE and immunoblot analysis after CSF fractionation via density flotation u ltracentrifugation. AD CSF was characterized by (i) increased sA beta and a po content of the HDL1, and (ii) sA beta association with apoE and apoJ in HDL2, HDL3 and very high density lipoproteins. The finding supports our pro posed hypothesis that upregulation of brain cholesterol dynamics is a funda mental event in the pathophysiology of AD and that sA beta binding to apo a nd lipid may have important structure-functional consequences. (C) 2001 Els evier Science Ireland Ltd. All rights reserved.