Biochemical characterization of Alzheimer's soluble amyloid beta protein in human cerebrospinal fluid: association with high density lipoproteins.
The soluble form of Alzheimer's amyloid beta protein (sA beta) is associated with high density lipoproteins (HDL) in normal human plasma (BBRC, 1994, 205, 1164-1171). Since sA beta is also present in cerebrospinal fluid (CSF) and the lipoprotein pattern of CSF is different from that of plasma, it was of interest to ascertain whether the interaction of sA beta with HDL also occurs in CSF. Normal human CSF lipoproteins were obtained by sequential flotation ultracentrifugation and analyzed for the presence of sA beta via immunoblot, size-exclusion chromatography, immunoelectron microscopy, N-terminal sequence and mass-spectrometry analyses. Soluble A beta was associated with CSF-HDL particles of 16.8 +/- 3.2 nm in diameter and approximately 200 kDa of relative molecular mass. A approximately 4.3 kDa component purified by HPLC was immunoreactive with anti-A beta antibodies and exhibited an N-terminal sequence identical to the A beta peptide with a mass of 4325.1 Da, indicating that the main sA beta specie associated with CSF-HDL is A beta 1-40.
Koudinov
A R
AR
Department of Pathology, New York University Medical Center, New York 10016, USA. koudinov@mchip00.med.nyu.edu
Koudinova
N V
NV
Kumar
A
A
Beavis
R C
RC
Ghiso
J
J
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid* / Q000302:isolation & purification; D000911:Antibodies, Monoclonal; D002784:Cholesterol / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D008075:Lipoproteins, HDL / Q000134:cerebrospinal fluid* / Q000737:chemistry / Q000648:ultrastructure; D053440:Lipoproteins, HDL3; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014280:Triglycerides / Q000097:blood
D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D008075:Lipoproteins, HDL; D053440:Lipoproteins, HDL3; D014280:Triglycerides; D002784:Cholesterol