IngentaConnect Alzheimers Disease and Immunotherapy

Abstract:

Site-directed antibodies which modulate conformation of bgr

-amyloid peptide became the theoretical basis of the immunological approach for treatment of Alzheimer's disease (AD). Indeed, antibodies towards the EFRH sequence, located between amino acids 3-6 of the N-terminal region of Alzheimer's A bgr

P, found to be a key position in protein conformation modulation, suppress formation of bgr

-amyloid and dissolve already formed fibrillar amyloid. The performance of anti- bgr

-amyloid antibodies in transgenic mice models of AD showed they are delivered to the central nervous system (CNS), preventing and dissolving bgr

-amyloid plaques. Moreover, these antibodies protected the mice from learning and age-related memory deficits. Naturally occurring anti-A bgr

P antibodies have been found in human CSF and in the plasma of healthy individuals, but were significantly lower in AD patients, suggesting that AD may be an immunodeficient disorder. Active and / or passive immunization against bgr

-amyloid peptide has been proposed as a method for preventing and / or treating Alzheimer's disease. Experimental active immunization with A bgr

1-42 in humans was stopped in phase II clinical trials due to unexpected neuroinflammatory manifestations. Antibodies generated with this first-generation vaccine might not have the desired therapeutic properties to target the ‘;correct’; mechanism, however, new clinical approaches are now under consideration. Immunotherapy represents fascinating ways to test the amyloid hypothesis and offers genuine opportunities for AD treatment, but requires careful antigen and antibody selection to maximize efficacy and minimize adverse events.

Keywords: alzheimer disease; monoclonal antibodies; abp; immunotherapy; n-terminal region; amyloid plaque; immunodeficiency; neuroinflammation

Document Type: Review article

DOI: 10.2174/1567205043332126

Affiliations: 1: Department of Molecular Microbiology & Biotechnology, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Ramat Aviv, Tel-Aviv, P.O. Box 69978, Israel.

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Alzheimer's Disease and Immunotherapy