Title

Immunization in Alzheimer's Disease: Naive Hope or Realistic Clinical Potential

Document Type

Journal Article

Publisher

Nature Publishing Group

Faculty

Computing, Health and Science

School

Exercise, Biomedical and Health Science

RAS ID

8562

Comments

This article was originally published as: Foster, J. K., Verdile, G., Bates, K. A., & Martins, R. N. (2009). Immunization in Alzheimer's disease: naive hope or realistic clinical potential. Molecular Psychiatry, 14, 239-251. Original article available here

Abstract

There has been considerable recent interest in vaccination of patients by immunotherapy as a potentially clinically useful methodology for combating histopathological changes in Alzheimer's disease (AD). The focus of the majority of this research has been on (1) active immunotherapy using the pre-aggregated synthetic β-amyloid (Aβ) 42 preparation AN1792 vaccine (QS-21), or (2) passive immunization using injections of already prepared polyclonal anti-Aβ antibodies (intravenous immunoglobulin). These two clinical approaches to the treatment of patients with AD represent the focus of this review. We conclude here that, with certain caveats, immunization offers further potential as a technique for the treatment (and possible prevention) of AD. New studies are seeking to develop and apply safer vaccines that do not result in toxicity and neuroinflammation. Nevertheless, caution is warranted, and future clinical investigations are required to tackle key outstanding issues. These include the need to demonstrate efficacy in humans as well as animal models (especially with respect to the potentially toxic side effects of immunotherapy), and fine-tuning in safely guiding the immune response. The issue of defining necessary and sufficient criteria for determining clinical efficacy remains an additional important issue for future immunization trials. The vaccination methodology appears to offer substantial current promise for clearing both soluble and aggregated amyloid in AD. However, it remains to be determined whether this approach will help to repair already damaged neural systems in the disease, and the extent to which vaccination-driven amyloid clearance will impact beneficially on patients' neurocognitive capacity and their functional status. The outcomes of future studies will be important both clinically and scientifically: an important further test of the validity of the amyloid hypothesis of AD is to evaluate the impact of an effective anti-amyloid strategy on the functional status of patients with this disease.

DOI

10.1038/mp.2008.115

Access Rights

free_to_read

 

Link to publisher version (DOI)

10.1038/mp.2008.115