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Brain-imaging studies with a marker designed to detect amyloid also revealed that the people with the disease-linked mutation had higher levels of the protein in their brains. All three of these changes—low amyloid and high tau in the CSF, and high levels of amyloid in the brain—are also evident in people with the disease.

Researchers involved in the DIAN study are already preparing to test drugs designed to prevent the disease in this group of patients. “If we know people will get the disease and about when, perhaps we can treat them before they get the symptoms,” says Bateman. Examining changes in the newly identified markers will help them assess whether a particular treatment is working without having to wait 20 years for the outward onset of disease.

Bateman and others are working with pharmaceutical companies to compile a list of the most promising experimental treatments; 11 compounds have been nominated so far. The group is focusing on drugs designed to dampen amyloid production or deposition, since this is a key early factor in the inherited form of the disease. “If we can normalize these initial steps, perhaps we can prevent downstream events from occurring and ultimately prevent dementia,” says Bateman.

He says treatments that slow the inherited form are likely to be effective in the more common form as well. “Data strongly suggests that the two diseases share a common pathway,” he says. “If we can prevent Alzheimer’s disease in this group, we hope we can translate over into preventing Alzheimer’s in other individuals that are already on this pathway.”

Bateman draws an analogy to atherosclerosis, or hardening of the arteries, and heart attacks; people who have heart attacks often have increased atherosclerosis. Treatment with statins, which were developed to treat high cholesterol by reducing atherosclerosis, can also decrease the risk of a heart attack.

However, it’s not yet clear whether the early markers identified in the DIAN study are similarly detectible in people who will go on to develop common late-onset Alzheimer’s. These studies are much more difficult to conduct, given the difficulty of predicting who will develop the most common form of the disease.

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Credit: Journal of Neuroscience

Tagged: Biomedicine, Alzheimer's, brain imaging, prediction markets

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