Years before one of the key Alzheimer’s proteins show up in a patient’s brain scan, a test developed at the University of Pittsburgh can detect small amounts of it in spinal fluid. New research published in "Nature Medicine" suggests the findings could lead to earlier diagnoses and better treatment for the disease.
Two of the proteins that build up abnormally in the brain of an Alzheimer’s patient are amyloid beta — which form plaques around brain cells — and tau — which form tangles within brain cells. Together the proteins build up and suffocate neurons, which leads to brain atrophy and cognitive decline.
Pitt’s new biomarker test can detect traces of the lesser-understood tau protein, which emerging research has found to be more closely linked with cognitive impairment, sooner than a brain scan.
“Our test identifies very early stages of tau tangle formation — up to a decade before any tau clumps can show up on a brain scan,” said senior author Thomas Karikari, Ph.D., assistant professor of psychiatry at Pitt. “Early detection of tangle-prone tau could identify the individuals who are likely to develop Alzheimer’s-associated cognitive decline and could be helped with new generation therapies.”
In the absence of a cure, early Alzheimer’s diagnosis is critical as it grants patients the chance to plan for the future and access treatments to manage their symptoms.
Researchers followed Alzheimer’s patients during the final years of their life and evaluated their brains after they died. They also followed patients still living who were evaluated with brain scans and the spinal fluid test.
As one of the oldest states in the country, 11.5% of Pennsylvanians aged 65 and older have Alzheimer’s disease, which is higher than the national average of 10.9%. A report by the Alzheimer’s Association last year found that more than 280,000 elderly Pennsylvanians have the disease.
Since amyloid clusters appear first during the degenerative process, Alzheimer’s research has historically emphasized treating the plaque around the cell instead of the tau building up inside of it. But Karikari said those treatments don’t work once the brain has a buildup of tau.
“When you have tau, the amyloid therapies have much less chance to work well to be efficient,” Karikari said. “Once the tau tangles light up on a brain scan, it may be too late to put out the fire and their cognitive health can quickly deteriorate.”
And since many elderly adults with a buildup of amyloid-beta in their brains never go on to develop the cognitive symptoms of Alzheimer’s, scientists are beginning to focus more on targeting the tau protein.
Karikari’s research pinpointed a core region of the tau protein that causes it to tangle up in the brain cell. Two sites identified by the team were able to indicate the early stages of tau-clumping, which could inform new intervention strategies to prevent the clusters.
“As long as you have tau pathology in the brain, this marker was able to tell,” he said.
Since tau protein therapy is still in its infancy, Karikari’s findings could provide a roadmap for future treatments. In its next phase, Pitt’s research will develop a blood test to detect both tau and amyloid proteins.
The findings published in "Nature Medicine" were part of a collaboration with nearly 30 researchers across several institutions including Pitt, the University of Gothenburg in Sweden as well as the University of Warwick and University College in the United Kingdom.