Immunological approaches as therapy for Alzheimer's disease

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