Alzheimer's amyloid beta interaction with normal human plasma high density lipoprotein: association with apolipoprotein and lipids.
We report studies of the interaction of Alzheimer's amyloid beta protein (A beta) with normal human plasma high density lipoprotein (HDL), aiming to clarify to which lipoprotein (LP) structural constituent (apolipoprotein or lipid) soluble A beta is primarily bound. Purified HDLs were incubated with biotinylated A beta 1-40 followed by LP repurification by size exclusion (SE) HPLC. SDS-PAGE, immunoblot and N-terminal sequence analysis of the biotin-A beta positive protein bands revealed that A beta is bound to many apolipoproteins of the HDL, mainly apoA-I, apoA-II, apoE and apoJ. On the other hand, reconstituted, protein-free HDL lipid particles also bind A beta peptide and inhibit its aggregation, as intact HDL does. This was assessed by SE-HPLC, SDS-PAGE, immunoblot analysis, ultrastructural electron microscopy and Congo Red staining for beta amyloid fibrils. Our data imply that A beta binding to lipids may play an important role in maintaining the peptide in solution and thus be particularly relevant to A beta normal and pathologic biochemistry and physiology.
Koudinov
A R
AR
Russian Academy of Medical Sciences, Russian Peoples' Friendship University School of Medicine, Moscow, Russia. koudin@imb.imb.ac.ru
Berezov
T T
TT
Kumar
A
A
Koudinova
N V
NV
D000328:Adult; D000544:Alzheimer Disease; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D001053:Apolipoproteins / Q000097:blood* / Q000737:chemistry; D001665:Binding Sites; D019921:Biotinylation; D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D015151:Immunoblotting; D008055:Lipids / Q000097:blood* / Q000737:chemistry; D008075:Lipoproteins, HDL / Q000097:blood*; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D017421:Sequence Analysis
D016229:Amyloid beta-Peptides; D001053:Apolipoproteins; D008055:Lipids; D008075:Lipoproteins, HDL