Biochemical Characterization of Alzheimer's Soluble Amyloid Beta Protein in Human Cerebrospinal Fluid: Association with High Density Lipoproteins

Abstract

The soluble form of Alzheimer's amyloid β protein (sAβ) is associated with high density lipoproteins (HDL) in normal human plasma (BBRC,1994,205,1164–1171). Since sAβ 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 sAβ with HDL also occurs in CSF. Normal human CSF lipoproteins were obtained by sequential flotation ultracentrifugation and analyzed for the presence of sAβ via immunoblot, size-exclusion chromatography, immunoelectron microscopy, N-terminal sequence and mass-spectrometry analyses. Soluble Aβ was associated with CSF-HDL particles of 16.8 ± 3.2 nm in diameter and approximately 200 kDa of relative molecular mass. A ∼4.3 kDa component purified by HPLC was immunoreactive with anti-Aβ antibodies and exhibited an N-terminal sequence identical to the Aβ peptide with a mass of 4325.1 Da, indicating that the main sAβ specie associated with CSF-HDL is Aβ1-40.