Using a new mouse model of Alzheimer’s disease, researchers have found that Alzheimer’s pathology originates in Amyloid-Beta (Abeta) oligomers in the brain, rather than the amyloid plaques previously thought by many researchers to cause the disease.
“The buildup of amyloid plaques was described over 100 years ago and has received the bulk of the attention in Alzheimer’s pathology,” said lead author Sam Gandy. “But there has been a longstanding debate over whether plaques are toxic, protective, or inert.”
Several research groups had previously proposed that rather than plaques, floating clumps of amyloid (called oligomers) are the key components that impede brain cell function in Alzheimer’s patients.
To study this, the researchers developed a mouse that forms only these oligomers, and never any plaques, throughout their lives.
They found that the mice that never develop plaques were just as impaired by the disease as mice with both plaques and oligomers. Moreover, when a gene that converted oligomers into plaques was added to the mice, the mice were no more impaired than they had been before.
“These findings may enable the development of neuroimaging agents that visualize or detoxify oligomers,” said Dr. Gandy. “New neuroimaging agents that could monitor changes in Abeta oligomer presence would be a major advance. Innovative neuroimaging agents that will allow visualization of brain oligomer accumulation, in tandem with careful clinical observations, could lead to breakthroughs in managing, slowing, stopping or even preventing Alzheimer’s.
“This is especially important in light of research reported in March showing that 70 weeks of infusion of the Abeta immunotherapeutic Bapineuzumab® cleared away 25 percent of the Abeta plaque, yet no clinical benefit was evident.”
References:
1. Sam Gandy, et al. Days-to-criterion as an indicator of toxicity associated with human Alzheimer amyloid- oligomers. Annals of Neurology, 2010; DOI: 10.1002/ana.22052
