Lemere C.A.,New Research Building 636F |
Masliah E.,University of California at San Diego
Nature Reviews Neurology | Year: 2010
Alzheimer disease (AD) is the most common form of dementia. The amyloid-Β (AΒ) peptide has become a major therapeutic target in AD on the basis of pathological, biochemical and genetic evidence that supports a role for this molecule in the disease process. Active and passive AΒ immunotherapies have been shown to lower cerebral AΒ levels and improve cognition in animal models of AD. In humans, dosing in the phase II clinical trial of the AN1792 AΒ vaccine was stopped when 6% of the immunized patients developed meningoencephalitis. However, some plaque clearance and modest clinical improvements were observed in patients following immunization. As a result of this study, at least seven passive AΒ immunotherapies are now in clinical trials in patients with mild to moderate AD. Several second-generation active AΒ vaccines are also in early clinical trials. On the basis of preclinical studies and the limited data from clinical trials, AΒ immunotherapy might be most effective in preventing or slowing the progression of AD when patients are immunized before or in the very earliest stages of disease onset. Biomarkers for AD and imaging technology have improved greatly over the past 10 years and, in the future, might be used to identify presymptomatic, at-risk individuals who might benefit from AΒ immunization. © 2010 Macmillan Publishers Limited. All rights reserved.