Immunological approaches as therapy for Alzheimer's disease

The pathology of Alzheimer's disease (AD) shows a significant correlation between beta-amyloid peptide (AbetaP) conformation and the clinical severity of dementia. For many years, efforts have been focused on the development of inhibitors of beta-amyloid (Abeta) formation and its related neurotoxic effects. The author has developed a new concept showing that site-directed antibodies may modulate formation of Abeta. The performance of anti-Abeta antibodies in transgenic mice models of AD showed that they are delivered to the central nervous system (CNS), preventing in vivo formation of Abeta. Moreover, these antibodies dissolve Abeta plaques and protect the mice from learning difficulties and age-related memory deficits. Experimental active immunisation with Abeta (1-42) in humans has been stopped in Phase II of their clinical trials. However, several new preparations, able to provide antibodies against Abeta by either active or passive routes, have been formulated and at least one of these is likely to reach clinical testing. These data support the hypothesis that AbetaP plays a central role in AD and antibodies which modulate Abeta conformation may lead to immunotherapy of the disease.