AMYLOID CLEARING IMMUNOTHERAPY FOR ALZHEIMER'S DISEASE AND THE RISK OF CEREBRAL AMYLOID ANGIOPATHY.

Abstract

Immunization strategies which aid in the clearance of beta-amyloid (Aβ) plaques have raised new hopes for the treatment of Alzheimer's disease (AD). Two particularly promising passive immunization therapies currently being investigated include intravenous immunoglobulins (IVIG) containing Aβ antibodies and specifically developed monoclonal antibodies for Aβ. These Aβ antibodies may reduce amyloid accumulation in the brain by binding to the amyloid peptide and drawing it in through the blood-brain barrier for subsequent removal from the capillaries. However, as this strategy aims at removing extracellular amyloid through cerebral vessels, a redistribution of amyloid pathology may manifest as increased cerebral amyloid angiopathy (CAA). CAA occurs when Aβ becomes embedded in the walls of cerebral vessels associated with weakening of the vessel walls. Antibody mediated Aβ clearance from the parenchyma could significantly increase the Aβ burden in the vessel lumen and wall, therefore increasing the risk of vessel rupture and hemorrhage. This chapter will review the current literature on Aβ immunotherapy for AD and explore the mechanisms as well as possible risks of amyloid clearance treatment, particularly cerebral amyloid angiopathy.