Peptide Immunization As A Potential Therapy For Ad

In this first study, the investigators documented significant prevention of plaque formation in the immunized mice. This was a very exciting finding concerning a new potential therapy for AD—immunization with Aß, letting the body's normal immune response do the rest.

How does the immunization effect a decrease in amyloid plaque formation? These immunization procedures produce active anti-Aß antibodies in the bloodstream, a fraction of which apparently can penetrate into the CNS. The idea is that microglia in the CNS clear the antibody- Aß complexes, reducing Aß burden. Alternatively, decreased Aß in the bloodstream resulting from immune clearance outside the brain may result in lowered CNS Aß levels, by passive diffusion of the Aß peptide out of the CNS.

A year later two groups continued these efforts and published further exciting and encouraging results. Janus et al. (93) and Morgan et al. (94) both reported ameliorative effects of the immunization protocol on the development of aging-related deficits in learning and memory in AD mouse models as well. This took the observations to the next level, demonstrating important symptomatic relief, as least as assessed using the tools available currently. Also encouraging was that similar results were obtained using a variation of the immunization approach. "Passive" immunization involves the perfusion of previously isolated and purified antibodies into the test subject. Like the active immunization studies described previously, passive immunization with anti-Aß antibodies similarly improves memory performance in AD model mice (95, 96).

Overall these findings precipitated great hope that an immunization approach might prove of practical utility in humans. Work in this area is unfortunately at somewhat of a standstill at present. Pilot immunization studies in normal humans indicated no deleterious effects of Ap immunization. However, in the initial study of immunization therapy using human AD patients, a small number of study subjects developed brain inflammation. This side effect, while perhaps not entirely unexpected, necessitated a halt of the study and, at present, a moratorium on this specific line of human studies.

The potential of immunotherapy as an effective treatment for Alzheimer's disease is one of the most exciting developments in the recent history of Alzheimer's disease research, offering real hope for effective therapy in the aging human. However, at present it is clear that significant work lies ahead in evaluating whether the approach will be adaptable to the human clinically.

There is an additional reason to highlight these studies, independent of their significance as a potential new therapeutic approach. As we discussed in the main text, much work is currently underway aimed at testing various predictions of the amyloid beta hypothesis of AD. The behavioral studies with Ap immunization test one key prediction of this hypothesis— the block prediction. The observation that decreasing Ap burden in the CNS ameliorates behavioral deficiencies is strong support for the hypothesis that Ap is a causative agent in the memory defects associated with early AD.

Brain Battalion

Brain Battalion

Get All The Support And Guidance You Need To Be A Success At Beefing Up Your Brain. This Book Is One Of The Most Valuable Resources In The World When It Comes To Understanding Your Brain to Come Up With A Battle Plan For Intelligence.

Get My Free Ebook

Post a comment