Alzheimer’s disease protein flows through brain’s neurons

Alzheimer’s appears to spread through the brain like poison in a river, according to a study that's the first to track the destruction caused by an abnormal protein implicated in the disease. Researchers created genetically engineered mice with abnormal tau protein in the brain’s entorhinal cortex, the first place the substance shows up in people with Alzheimer’s, according to a paper in the journal PLoS One. From there, they mapped the mouse brains over 22 months as the tau spread across neurons within the organ to other regions.Tau is one of two abnormal proteins tied to Alzheimer’s. The one more closely associated is beta amyloid, which can be detected using imaging tools. While high levels of beta amyloid can predict risk, the amount of tau found after death correlates more closely with dementia, said Karen Duff, the lead researcher. Knowing the path tau takes in the brain may one day improve treatment, she said.“There may be an intervention point that might prevent dementia” if scientists can figure out how to stop the tau from spreading, said Duff, who is a professor of pathology at Columbia University Medical Center.The place where abnormal tau shows up earliest isn’t associated with dementia at all, she said.Tau also is involved in other kinds of dementia, including frontotemporal lobe dementia, Parkinson’s disease and Lewy body disorder, Duff said. The spread is probably similar even if the abnormal protein arises somewhere else in the brain.Tau-Amyloid Interaction It’s not clear from the research how tau and amyloid interact, a question Duffy said she wants to study further.When tau is normal, it supplies nutrients to nerve cells in the brain. When it is damaged, it becomes tangled and shuts off nutrients, causing the death of brain cells.Beta amyloid is known to play a role in Alzheimer’s in part because genes that confer higher risks of the illness have to do with amyloid, Duff said. Today’s research suggests that it somehow interacts with the tau that ultimately kills the cells.“There’s some interaction, and it seems amyloid has its detrimental effects through tau,” Duffy said. “There’s an interaction at a fundamental level we don’t understand yet."Closer study of the mouse model, as well as imaging tools that would allow scientists to see tau accumulate in living humans’ brains, would be helpful, she said.The mice may also prove useful for testing interventions to prevent the spread of the abnormal clumps of protein, she said.“Mostly we wanted to mimic the early stages of Alzheimer’s, because that could best give us some idea of where we could target therapeutically,” Duff said. “And if we layer on an amyloid model, we may also be able to see interactions.”TauRX Pharmaceuticals Ltd., a closely held Singaporean drugmaker, is working on an Alzheimer’s treatment based on tau, and agreed in June 2010 to collaborate with German drugmaker Bayer AG to make an imaging test for the tau protein clumps.