AB42 Immunisation Clears Brain Plaques, Does Not Prevent Dementia in Alzheimer's

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Title: AB42 Immunisation Clears Brain Plaques, Does Not Prevent Dementia in Alzheimer's
URL: http://www.pslgroup.com/dg/225F1E.htm
Doctor's Guide
July 17, 2008

NEW YORK -- July 17, 2008 -- Although immunisation against the amyloid-beta peptide 42 (AB42) can clear amyloid plaques in the brain, it does not prevent the progressive neurodegeneration associated with Alzheimer's disease, according to a study in this week's Dementia Special Issue of The Lancet.

Clive Holmes, PhD, Memory Assessment and Research Centre, Moorgreen Hospital, Southampton, United Kingdom, and colleagues did a follow-up of a randomised, placebo-controlled, phase 1 trial on amyloid-beta immunisation to determine the long-term effect, if any, of the procedure on patients' brain function.

The study analysed 80 patients with Alzheimer's disease who had all been enrolled in a trial of immunisation with AB42 in September 2000, with the follow-up study completed by September 2006.

Of the patients, 64 were given the vaccine and 16 received placebo. Before follow-up, 20 patients died (15 from the immunised group, 5 from the placebo group) and 22 patients died (19 immunised group, 3 placebo group) during follow-up.

Of the deceased, 9 had given permission for postmortem, and all were from the immunised group. Researchers analysed 8 of the 9 deceased and found all 8 to have lower amyloid-beta load (2.0%) compared with controls (5.1%).

Although there was considerable variation in amyloid-beta load and degree of plaque removal among immunised participants, the degree of plaque removal correlated with the mean antibody response attained during the study period.

Seven of the 8 immunised patients who underwent postmortem, including those with virtually complete plaque removal, had severe end-stage dementia before death. Across the whole study group, the researchers found no evidence of improved survival or increased time to severe dementia in the immunised group versus the placebo group.

"Despite the evidence of disease modification, there is little evidence to suggest that there is any major effect on cognitive function," the authors wrote.

"All but 1 of the individuals who died during the follow-up phase had clear end-stage dementia before death, including the 2 individuals with highest mean antibodies to amyloid-beta and almost complete elimination of plaques. These findings imply that progressive neurodegeneration can occur in Alzheimer's disease despite removal of plaques."

In an accompanying comment, Peter St. George-Hyslop, MD, Department of Clinical Neurosciences, University of Cambridge, United Kingdom, and John C. Morris, MD, Centre for Research in Neurodegenerative Diseases and Toronto Western Hospital, University of Toronto, Toronto, Ontario, said that further clinical trials that can detect even small changes in disease progression are necessary and that the future of anti-amyloid therapies could see them given in advance as a prophylactic long before the onset of symptoms in people at risk of the disease.

SOURCE: The Lancet

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