Effect of cerebrospinal fluid from normal and Alzheimer's patients with different apolipoprotein E phenotypes on in vitro aggregation of amyloid beta-protein.

We examined the effect of cerebrospinal fluid (CSF) from 23 Alzheimer's disease (AD) patients and 22 age-matched non-demented controls with apolipoprotein E4/4, 3/3, or 3/2 phenotypes on in vitro aggregation of amyloid beta-protein (A beta) 1-40 by Thioflavin T fluorescence spectroscopy. CSF from both AD and control groups inhibited A beta aggregation, as compared to that of phosphate buffered saline, in agreement with an earlier report (Wisniewski et al., 1993). However, there was significantly less aggregation of A beta in presence of CSF from AD than that from non-demented controls. The presence of CSF from controls with apoE3/3 phenotype resulted in higher A beta aggregation as compared to other phenotypes. There was a positive correlation between CSF apoE concentrations and A beta aggregation; whereas age, CSF soluble A beta levels or severity of dementia did not correlate with A beta aggregation. These results suggest that mechanism of sequestration of A beta in CSF may not be defective in AD. Amyloid formation in AD may be impact of altered balance of other factors such as amyloid-associated proteins/extracellular matrix components that can immobilize A beta in the brain, and promote its fibrillogenesis in AD.