Cognitive Clog

The paper:

The finding:
James Cleary at the Minneapolis VA Medical Center and colleagues revealed that soluble human forms of amyloid-β oligomer (a-β), a protein implicated in Alzheimer disease, disrupted rats' memory of a learned lever-pressing task. "We didn't see any neurotoxicity, yet we saw cognitive deficits show up shortly after we gave them [the a-β]," Cleary says. The effect went away within just a few hours. "If you tested the animal again a day later, it was able to do the task beautifully," says coauthor Dennis Selkoe.

The significance:
While previous studies had found cognitive impairments from mixtures of synthetic fibrils, monomers, and oligomers, the effects on cognition of the isolated form of a-β oligomers had never been characterized. "I think it was an important step in understanding what assembly state [of a-β] impairs cognition," says Lennart Mucke from the Gladstone Institute of Neurological Disease.

The catch:
The presence of a-β oligomers might later lead to neurodegeneration, but the pathology is still unclear. "Does this have anything to do with human Alzheimer's disease? We have a disconnect here," says Todd Golde from the Mayo Clinic. The authors agree that findings from the study do not exclude the possibility that other forms of a-β have a role in Alzheimer disease.

The future:
Cleary and colleagues are collaborating to further characterize synthetic, brain-derived, and cell-derived oligomers and their behavioral effects. Compounds that block a-β oligomers may be able to reverse or delay some cognitive impairment, Mucke says.