More and more evidence shows that Alzheimer's disease, one of the most perplexing medical problems, belongs to a large group of etiologically diverse neurodegenerative disorders, so-called 'conformational' diseases. Pathology of Alzheimer's disease (AD) shows significant correlation between β-amyloid peptide (A↑P) deposition and the clinical severity of dementia. For many years efforts have been focused on the development of selective inhibitors of amyloid formation to reduce the extent of its deposition and related neurotoxic effects. We developed a new concept showing that site-directed antibodies may modulate the conformation of β-amyloid peptide, thus leading to immunological treatment of Alzheimer's disease as well as of other conformation related diseases. Indeed, antibodies toward the EFRH sequence, located between amino acids 3-6 of the N-terminal region of Alzheimer's AβP, found to be a key position in protein conformation modulation, suppress formation of β-amyloid and dissolve already formed fibrillar amyloid. Performance of such anti-β-amyloid antibodies in transgenic mice models of AD showed that they are delivered to the central nervous system (CNS), preventing formation of β-amyloid and dissolving real plaques. These data support the hypothesis that AβP plays a central role in AD, and antibodies that modulate Aβ conformation may lead toward immunotherapy of the disease.
- Conformational diseases