Immunotherapy for Alzheimer‘s Disease

Abstract

Patients with Alzheimer's disease (AD) express severe cognitive deficiencies with a concurrent increase in brain deposits of aggregated amyloid-beta (Abeta), a catabolic derivative of the ubiquitous amyloid precursor protein (APP). Interference in the homeostasis of Abeta has been suggested as a treatment for AD patients. In AD murine models it has been shown that active and passive immunization against Abeta alters the equilibrium of the different forms of Abeta in brain and serum, leading to a concomitant cognitive improvement. Generally, the clinical trials that followed the study of the murine AD model confirmed the results of the AD models, although safety issues advocate the passive vaccination approach rather than the active one. However, passive vaccination of patients with monoclonal antibodies derived from nonhuman sources is limited. Anti-Abeta IgM and IgG antibodies, which are present in the serum of every healthy individual and probably play a role in the homeostasis of Abeta in healthy subjects, might be beneficial to AD patients, as shown for the effect exerted by the commercial preparation of intravenous immunoglobulin. Human monoclonal anti-Abeta antibodies, which correspond to the ubiquitous anti-Abeta antibodies, are plausible candidates for future immunotherapy of AD patients.