期刊
NATURE REVIEWS NEUROLOGY
卷 6, 期 2, 页码 108-119出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nrneurol.2009.219
关键词
-
资金
- NIH [R01AG20159, AG5131, AG18440, AG02074, AG10435]
Alzheimer disease (AD) is the most common form of dementia. The amyloid-beta (A beta) 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 A beta immunotherapies have been shown to lower cerebral A beta levels and improve cognition in animal models of AD. In humans, dosing in the phase II clinical trial of the AN1792 A beta vaccine was stopped when similar to 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 A beta immunotherapies are now in clinical trials in patients with mild to moderate AD. Several second-generation active A beta vaccines are also in early clinical trials. On the basis of preclinical studies and the limited data from clinical trials, A beta 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 A beta immunization.
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