Even in the prime of life, although still healthy and intelligent, our brains can secretly develop the deadly plaques and tangles of Alzheimer’s disease. The first sign of trouble is memory loss and at that point the damage is done.
But innovative new blood tests can now detect these hidden signs of illness, years before heartbreaking symptoms appear.
The tests are not yet recommended for generalized general public screening, as improvements are needed. But recently released data on the first FDA-approved version from C2N Diagnostics shows it’s 81 percent accurate in identifying levels of a brain protein that’s a hallmark of Alzheimer’s disease. For the first time, the test is being used in a major drug study funded by the National Institutes of Health in 75 medical centers.
“When is the best time to put out a fire? When does it start, ”said Dr. Julio Rojas-Martinez of the Memory and Aging Center at UC San Francisco, who uses the test to identify people as young as 55 to participate in NIH’s AHEAD study, aimed at find drugs to delay memory loss before symptoms. to start.
Once refined and more widely available, he said, these blood tests “will be revolutionary in that we can detect who is at risk.” While current drugs can only delay cognitive decline, not prevent it, it would allow people to enroll in research trials as early as possible.
Alzheimer’s disease, the most common form of dementia in older people, is a brain disorder that slowly destroys memory, thinking skills, and even the ability to perform even the simplest of tasks. According to the Alzheimer’s Association, it affects one in nine people over the age of 65.
As long as two decades before symptoms, we build up toxic levels of proteins, called amyloid and tau, which form plaques and tangles.
Memory loss occurs after once healthy brain cells stop functioning, lose their connections, and die.
Currently, the disease is diagnosed by memory tests by a trained neurologist and then confirmed by an expensive positron emission tomography (PET) scan of the brain or an invasive lumbar puncture to obtain cerebrospinal fluid. Although genetic tests can help predict risk, they do not describe the dynamic state of a brain.
“Very often people are not identified as having Alzheimer’s disease or a related disorder,” said Elizabeth Edgerly, director of the Alzheimer’s Association of Northern California and Northern Nevada. “The diagnostic process can be a challenge. “
At 58, “I definitely had memory problems, but people kind of ignored it,” said Pam Montana, now 66, of Danville, a former sales manager at Intel whose the agile mind could no longer memorize complex engineering concepts. Words come easily to her, but when she met her staff, she read notes to make sure they were correct.
“The diagnosis was really a struggle for me,” she said. “I’m talkative, I had a nice outfit and makeup on, and they said ‘You look beautiful.’ Everyone thinks Alzheimer’s is a grandmother in a wheelchair.
It wasn’t until a routine conversation at the doctor’s office – when she couldn’t remember where she had graduated from college – that the alarms went off.
His diagnosis was then confirmed by a high-tech PET scan, which involves an injection of radiolabeling fluid and remains motionless in a long tube. A diagnosis can be even more difficult if a patient does not have access to medical specialists and high-tech tests.
“If there was someone who could just draw my blood and say, ‘Yes, you have this, or you have that,’ then we could go from there,” she said.
With so few treatments available for this debilitating disease, why might a test be helpful?
“Early diagnosis is extremely helpful for several reasons,” said Lena Chow of Palo Alto, who cared for her late husband Bob Kuhar, a long-distance runner and engineer with a doctorate in clinical psychology. “There are lifestyle changes and many strategies, like socialization programs, to improve the quality of life. There are also pragmatic reasons, like the withdrawal of the driving license, for safety reasons. “
A major breakthrough in Alzheimer’s disease research laid the foundation for testing: the so-called “biomarker revolution,” which detected plaques and tangles. A test measures biomarkers that enter the bloodstream.
But reliability has proven elusive. Due to the blood brain barrier, biomarkers could not be found in sufficient quantity. And blood is a soup of many different substances, so traditional tools have given inconsistent results.
Now, with the advent of better analytical techniques, even small amounts of these biomarkers can be detected.
“Our big leap was to detect these small molecules with very low concentrations in plasma,” said Rojas-Martinez. The new tests “are 1,000 times more sensitive. This is what makes this business possible.
The most immediate application is for research. If patients could be identified quickly and easily, it would reduce the cost of drug trials. Billions of dollars have been spent designing treatments, with next to nothing to show.
“A blood test is so much more affordable and more easily accepted,” Edgerly said.
The tests are not yet ready for general use. This is because more work is needed to assess their performance in real clinical settings. And some clinicians question the prognostic value, noting that people can live with plaques in the brain and never develop symptoms.
In addition, the analysis is technically difficult. It requires a mass spectrometer and other specialized equipment. Blood samples require rapid centrifugation and freezing, procedures beyond the current capabilities of most average laboratories. Collection techniques should be standardized.
But companies are rushing to create simpler, cheaper, and easier tests that are suitable for widespread clinical use. Some people look for signs of amyloid; others, tau; still others, the relationship of the two.
Testing will continue to improve, Rojas-Martinez said. But until then, “our priority should be providing care, helping the family prepare and plan for the future.”
For now, the C2N Diagnostics test is the only one available, on prescription from a doctor. But at least eight more tests – by the companies Quanterix, Roche, Eli Lilly, ADx, Shimadzu, MagQu, Janssen and Fujirebio – are in the works.
“Over the next year or so, a test might be readily available,” Edgerly predicted. “And that would be a game changer.”