Glycosaminoglycan mimetics: a therapeutic approach to cerebral amyloid angiopathy

Amyloid deposits characteristic of cerebral amyloid angiopathy lead to vess el rupture and intracerebral hemorrhage. Proteoglycans associate with the a myloid fibril deposits and are thought to play a role in the polymerization of amyloid proteins and the propagation of the deposition process. A serie s of low molecular weight anionic compounds was developed to mimic the glyc osaminoglycan moieties of these proteoglycans. These compounds were tested in different in vitro systems to determine their anti-A beta amyloid activi ty Specific compounds were identified as being anti-fibrillogenic and prote ctive against A beta -induced cytotoxicity. Such compounds also did not sho w intrinsic cellular toxicity, could cross the blood-brain barrier (BBB) in vivo, and showed a good safety profile following chronic exposure. Molecul es showing an anti-amyloid profile combined with the ability to cross the B BB represent promising therapeutics for CAA.