Experimental Alzheimer鈥檚 vaccines might work by generating antibodies that draw key brain proteins into the blood, rather than entering the brain themselves, new research suggests. The finding should lead to more effective Alzheimer鈥檚 treatments in the future, the researchers say.
One of the earliest changes in the brain of an Alzheimer鈥檚 patient is the appearance of plaques of amyloid beta (a-beta) peptides. Elan Pharmaceuticals, based in Ireland, is currently testing an a-beta vaccine in Alzheimer鈥檚 patients with moderate memory impairments. Previous research found that the vaccine cleared plaques in mice brains.
快猫短视频s thought that the vaccine worked by triggering the production of antibodies, which entered the brain and destroyed the plaques. But when a team led by David Holtzmann at Washington University, US, injected mice with anti-amyloid beta antibodies, they found the blood concentration of the peptides shot up.
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鈥淲ithin hours of injecting the antibody into the mice, the concentration of amyloid-beta in the bloodstream rose approximately 1,000 times higher than it had been before the injection,鈥� Holtzmann says.
Blood-brain barrier
鈥淥ur studies indicate that the level of certain peptides in the brain might be able to be modified by drugs or treatments that don鈥檛 necessarily need to cross the blood-brain barrier,鈥� Holtzmann says.
But the team does not know exactly how the process of drawing the peptides into the blood should help destroy the plaques.
It is possible that pulling the peptides into the blood disrupts the plaques and causes them to break up, says Sangram Sisodia, an expert on Alzheimer鈥檚 disease at the University of Chicago. Alternatively, drawing enough of the protein out into the bloodstream so that the brain鈥檚 own a-beta disposal mechanisms can cope might explain the findings, he says.
Nose drops
Other research backs up the team鈥檚 work. Cynthia Lemere of Harvard University and her colleagues tested Elan Pharmaceuticals鈥� vaccine in a nose drop form on mice. After eight weeks, they found a 75 per cent reduction in plaque formation 鈥� but also a 33-fold increase in a-beta levels in the blood of the mice.
鈥淭hese results may indicate that the way the vaccine works, in part, is to clear the beta-amyloid from the brain into the bloodstream,鈥� Lemere says.
Holtzmann and Lemere presented their research at the annual meeting of the Society for Neuroscience in San Diego.