Prophylactic and therapeutic vaccines against Alzheimer's disease / 生物工程学报

ABSTRACT

Beta-amyloid(Abeta) immunization as vaccines has now become a promising approach for the prevention and treatment of Alzheimer's disease (AD)after its debut in 1999. Transgenic mouse models of AD that develop age-dependent Abeta deposition, damage to the neuropil, and behavioral deficits have enabled researchers to test if the approach can influence these AD-like pathologic changes in their brains. Active immunization with different forms of A beta and protocols have been shown to decrease brain Abeta deposition and improve cognitive performance in these mice models in the following studies. Although the phase II clinical trials of active immunization with Abeta(AN1792)were halted last year due to the occurrence of CNS inflammation in a small subset of patients, researchers found that strong humoral responses can be induced by the vaccination. Furthermore, the active immunization also brings an almost complete clearance of Abeta from much of the cerebral cortex. Abeta specific antibodies are believed to cross blood-brain barrier by minimal destroy of vascular wall where amyloid depositions exist. Three possible mechanisms on removal of Abeta deposition from brain have also been reviewed. Still some problems should be clarified before this strategy could be applied for clinical therapy. Whether vaccination will improve the cognitive decline in AD patients will depend upon clinical assessments, which was vital to destiny of the approach.