Alzheimer's amyloid β 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 (Aβ) with normal human plasma high density lipoprotein (HDL), aiming to clarify to which lipoprotein (LP) structural constituent (apolipoprotein or lipid) soluble Aβ is primarily bound. Purified HDLs were incubated with biotinylated Aβ1-40 followed by LP repurification by size exclusion (SE) HPLC. SDS-PAGE, immunoblot and N-terminal sequence analysis of the biotin-Aβ positive protein bands revealed that Aβ 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 Aβ 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 β amyloid fibrils. Our data imply that Aβ binding to lipids may play an important role in maintaining the peptide in solution and thus be particularly relevant to Aβ normal and pathologic biochemistry and physiology.