Amyloid deposits characteristic of cerebral amyloid angiopathy lead to vessel rupture and intracerebral hemorrhage. Proteoglycans associate with the amyloid fibril deposits and are thought to play a role in the polymerization of amyloid proteins and the propagation of the deposition process. A series of low molecular weight anionic compounds was developed to mimic the glycosaminoglycan moieties of these proteoglycans. These compounds were tested in different in vitro systems to determine their anti-Abeta amyloid activity. Specific compounds were identified as being anti-fibrillogenic and protective against Abeta-induced cvtotoxicity. Such compounds also did not show intrinsic cellular toxicity could cross the blood-brain barrier (BBB) in vivo, and showed a good safety profile following chronic' exposure. Molecules showing an anti-amyloid profile combined with the ability to cross the BBB represent promising therapeutics for CAA.