Cerebrospinal Fluid from Alzheimer's Disease Patients Promotes Amyloid β-Protein Oligomerization

Abstract

Oligomers of the amyloid β-protein (Aβ) play an important role in Alzheimer's disease (AD). We hypothesized that AD patients have a central nervous system environment that promotes Aβ oligomerization. We investigated the effect of cerebrospinal fluid (CSF) from 33 patients with AD and 33 age-matched, non-demented controls on oligomerization of Aβ_1-40 and Aβ_1-42 using the technique of photo-induced cross-linking of unmodified proteins. CSF inhibited oligomerization of both Aβ_1-40 and Aβ_1-42. This inhibitory effect was significantly weaker in AD patients than in non-demented controls. Our results indicate that AD patients have a CSF environment favorable for Aβ oligomerization.