Author: Beka Solomon

Source: Current Alzheimer Research, Volume 1, Number 3, August 2004 , pp. 149-163(15)

Publisher: Bentham Science Publishers

Abstract:

Site-directed antibodies which modulate conformation of -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 AP, found to be a key position in protein conformation modulation, suppress formation of -amyloid and dissolve already formed fibrillar amyloid. The performance of anti--amyloid antibodies in transgenic mice models of AD showed they are delivered to the central nervous system (CNS), preventing and dissolving -amyloid plaques. Moreover, these antibodies protected the mice from learning and age-related memory deficits. Naturally occurring anti-AP 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 -amyloid peptide has been proposed as a method for preventing and / or treating Alzheimer's disease. Experimental active immunization with A 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: http://dx.doi.org/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.

Publication date: 2004-08-01

More about this publication?

• Current Alzheimer Research publishes peer-reviewed frontier review and research articles on all areas of Alzheimer's disease. This multidisciplinary journal will help in understanding the neurobiology, genetics, pathogenesis, and treatment strategies of Alzheimer's disease. The journal publishes objective reviews written by experts and leaders actively engaged in research using cellular, molecular, and animal models. The journal also covers original articles on recent research in fast emerging areas of molecular diagnostics, brain imaging, drug development and discovery, and clinical aspects of Alzheimer's disease. Manuscripts are encouraged that relate to the synergistic mechanism of Alzheimer's disease with other dementia and neurodegenerative disorders. Book reviews, meeting reports and letters-to-the-editor are also published. The journal is essential reading for researchers, educators and physicians with interest in age-related dementia and Alzheimer's disease. Current Alzheimer Research provides a comprehensive 'bird's-eye view' of the current state of Alzheimer's research for neuroscientists, clinicians, health science planners, granting, caregivers and families of this devastating disease.

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