Alzheimer's disease begins to change the brain long before it affects memory and thinking.
So, researchers are developing a series of tests to detect these brain changes that include an increase in toxic proteins, inflammation, and damage to the relationships between brain cells.
The tests are dependent on biomarkers, shorthand for biological markers that signal steps along the progress of the disease. These new tests make Alzheimer's diagnosis more accurate and help drug companies test new drugs.
"For the future, we hope we may be able to use these biomarkers to stop or delay memory changes from ever occurrences," said Maria Carrillo, chief researcher of the Alzheimer's Association. (The association is a recent NPR sponsor.)
The first Alzheimer's biomarker test was approved by the Food and Drug Administration in 201
It is a dye called Amyvid that reveals lumps of a protein called amyloid. These amyloid plaques are a hallmark of Alzheimer's.
Before Amyvid came together, the disease involved a lot of guesses, Dr. Howard Fillit, Basic Director and Chief Scientist at Alzheimer's Drug Discovery Foundation.
"I can now send a patient down the block to the radiology office and within 24 hours with 98% security, I can tell people whether they have Alzheimer's disease," Fillit says.
The test costs thousands of dollars, however, partly because it requires a PET scan of the brain. Amyvid only reveals amyloid plaques, which are only one of the brain's changes associated with Alzheimer's.
So the Alzheimer's Drug Discovery Foundation has launched an attempt to accelerate the development of biomarkers that are cheaper and discover a wider range of brain transitions.
A promising test discovers protein tau that causes toxic tangles to form in brain cells.
"Tangles represent the dying neurons," says Fillit, which means that a biomarker for rope could diagnose Alzheimer's even more accurate. It can also help pharmaceutical companies assess experimental drugs for the purpose of removing the rope from the brain.
Several drug companies appear to receive FDA approval for injected dyes that reveal ropes in patients receiving PET scans.
Finally, researchers hope to use biomarkers in spinal fluid and blood to assess levels of both amyloid and tau in the brain. These tests promise to be easier for patients and cheaper to administer.
Although detecting amyloid and rope in the brain, it won't be enough, Fillit says. People can have a high level of both and still do well until there is something else in the brain: inflammation.
"It's like having the highest sensitivity computer up there and throwing coffee on it," Fillit says.
So researchers are working to identify biomarkers for inflammation.
They also work on a biomarker that indicates the health of synapses, the connections between brain cells.
Weak synapses are one of the safest signs of Alzheimer's, Fillit says. "So we fund a clinical trial at a company that will use this biomarker as a measure of how well their drug retains synapses in the hippocampus of people with Alzheimer's disease."
Biomarkers for Alzheimer's are still a work in progress. For example, they must be tested in many different populations.
"What can represent as a biomarker in a population cannot actually be true in another, and we have seen this in other diseases," said the Alzheimer's association Carrillo.
Moreover, biomarkers still do not offer a reliable way to measure a person's mental function. They only reveal brain changes that are associated with memory loss and difficulty in thinking.
Although over time, the arrival of new markers should make the treatment of Alzheimer's more like treating other diseases, Carrillo says.
"We treat high cholesterol to reduce the risk of that heart attack," she says. And one day it may be possible to reduce the risk of dementia by treating high levels of amyloid, rope or brain inflammation.
Copyright NPR 2019.