Oligomers of the amyloid beta-protein (Abeta) play an important role in Alzheimer's disease (AD). We hypothesized that AD patients have a central nervous system environment that promotes Abeta oligomerization. We investigated the effect of cerebrospinal fluid (CSF) from 33 patients with AD and 33 age-matched, non-demented controls on oligomerization of Abeta1-40 and Abeta1-42 using the technique of photo-induced cross-linking of unmodified proteins. CSF inhibited oligomerization of both Abeta1-40 and Abeta1-42. 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 Abeta oligomerization.