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 amyloid beta (sA beta) protein, a major constituent of amyloid deposits in Alzheimer's disease (AD), with normal blood, cerebrospinal fluid (CSF) and central nervous system high density lipoproteins (HDLs). The present report aimed to elucidate the pattern of sA beta and apolipoprotein (apo) distribution in AD CSF-HDL subfractions. We studied AD CSF-HDL subfractions by SDS/PAGE and immunoblot analysis after CSF fractionation via density flotation ultracentrifugation. AD CSF was characterized by (i) increased sA beta and apo content of the HDL(1), and (ii) sA beta association with apoE and apoJ in HDL(2), HDL(3) and very high density lipoproteins. The finding supports our proposed hypothesis that upregulation of brain cholesterol dynamics is a fundamental event in the pathophysiology of AD and that sA beta binding to apo and lipid may have important structure-functional consequences.
Koudinov
A R
AR
Institute of Biomedical Chemistry and National Mental Health Research Center, Russian Academy of Medical Sciences, Timoshenko St., 38-27, Moscow 121359, Russia. koudin@imb.ac.ru
Berezov
T T
TT
Koudinova
N V
NV
D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D001053:Apolipoproteins / Q000134:cerebrospinal fluid*; D001665:Binding Sites / Q000502:physiology; D001812:Blood-Brain Barrier / Q000502:physiology; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002784:Cholesterol / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D015151:Immunoblotting; D008075:Lipoproteins, HDL / Q000134:cerebrospinal fluid*; D058225:Plaque, Amyloid / Q000378:metabolism; D018110:Receptors, Lipoprotein / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology*
D016229:Amyloid beta-Peptides; D001053:Apolipoproteins; D008075:Lipoproteins, HDL; D018110:Receptors, Lipoprotein; D002784:Cholesterol