Comment ST. LOUIS — Joe knew something was wrong when his wife, an energetic nurse and mother of three, became forgetful in her early 60s. Four years ago, Lynn was diagnosed with dementia, but decided not to have a spinal tap that would have shown if Alzheimer’s was the cause. The couple chose to pursue a lifelong dream by purchasing a 40-foot RV and traveling to national parks in 35 states. “It was an adventure we could have together,” Joe said. Last year, the couple returned to their home near St. Louis. After contracting Covid-19, Lynn became increasingly angry and agitated. When a distraught Joe asked if there was anything he could do, his wife’s neurologist at Washington University in St. Louis suggested a new Alzheimer’s blood test to rule out other diseases. The test confirmed Lin, 68, has the fatal neurodegenerative condition, upsetting her husband but giving him some peace. “After 50 years together, she’s on her own journey and I can’t go on,” said Joe, who like other relatives and patients interviewed for this story, spoke on the condition that only his middle names be used. used to protect family privacy. Simple blood tests for Alzheimer’s disease, long sought by doctors and researchers, have come on the market, representing a potentially powerful tool for diagnosing the devastating memory-robbing disease that afflicts 6.5 million Americans. The tests detect tiny amounts of abnormal proteins in the blood, including a sticky version called amyloid beta, to determine whether the pathological features of Alzheimer’s are present in the brain. “If you asked me five years ago if we would have a blood test that could reliably detect plaques and tangles in the brain, I would have said it was unlikely,” said Gil Rabinovici, a neurologist at the University of California, San Francisco. . “I’m glad I was wrong about that.” In the coming years, blood tests could change the way Alzheimer’s is researched, diagnosed and treated, experts say. Already, the tests, which are mostly used in clinical trials, are speeding up research. In routine patient care, doctors can prescribe the tests, but this rarely happens, in part because of the lack of effective treatments for Alzheimer’s disease. Additionally, the tests, which cost hundreds of dollars or more, are often not covered by insurance. But many neurologists say it’s only a matter of time before the tests become more widely adopted, providing clarity on a disease that’s notoriously difficult to diagnose and helping determine which patients should get new treatments — if federal regulators approve treatments now under examination. However, the tests are sparking heated debate over scientific and ethical questions: Who should take them and when? How accurate are they? Do patients want to know if they have Alzheimer’s? Should people without symptoms be tested? Before prescribing the tests, many doctors say they want to see more data about their performance, given the high stakes. The blood tests are emerging at a time when major advances in treatment may be on the horizon. In September, data showed that an experimental drug, called lecanemab, modestly slowed cognitive and functional decline. The drug, from Japanese pharmaceutical company Eisai and its US partner Biogen, was the first Alzheimer’s drug to clearly slow the deterioration in a well-run clinical trial. The data has not been peer-reviewed and more information is expected later this month. The FDA is scheduled to decide whether to approve the drug by Jan. 6. The success of lecanemab has boosted hope for drugs that remove amyloid plaques from the brain. But in recent days, a Roche drug has failed in clinical trials, raising questions about the treatments. Results from an Eli Lilly drug are expected next year. If the FDA approves any of the new anti-amyloid treatments and Medicare then decides to cover them, demand for the drugs could increase. To prescribe them, doctors need to know whether patients have accumulations of abnormal proteins in their brains, because the drugs aren’t safe: They can cause safety problems, including brain bleeding and swelling. “If there is a treatment that clearly shows clinical benefit, the demand for these blood tests could skyrocket,” said Reisa Sperling, director of the Alzheimer’s Research and Treatment Center at Brigham and Women’s Hospital in Boston. Alzheimer’s disease testing and treatments—and their future—are inevitably intertwined, especially as the number of people with the disease is projected to increase. Unless medical breakthroughs change course, nearly 13 million people in the United States are expected to be living with Alzheimer’s by 2050, according to the Alzheimer’s Association. Globally, the number is predicted to be 153 million, according to research in the Lancet. Diagnosing Alzheimer’s disease is difficult, especially in the early stages. Brain autopsies are the only way to be sure the disease is present. Spinal taps and specialized PET scans are highly accurate at identifying biological changes – ‘biomarkers’ – that define the disease. However, spinal taps are invasive, and the scans, which can cost $5,000 or more, are not covered by Medicare except in trials. Most doctors rely on symptoms, cognitive tests, and other assessments to diagnose Alzheimer’s. In primary care, where most patients are assessed, more than half are misdiagnosed, research shows. Over the past 15 years, researchers have become increasingly interested in developing blood tests that provide a window into the brain. Today, three tests — from C2N Diagnostics, Quest Diagnostics and Quanterix — are on the market, with more on the way. C2N debuted in a trial two years ago, based on discoveries by scientists at the University of Washington. Tests from Quest and Quanterix entered the market this year. None are covered by Medicare. Other companies, including Eli Lilly and Roche, have developed tests or are working on them. Next generation tests are on the way. C2N charges $1,250 for its test and offers financial assistance to qualifying patients. Quest, which charges $500, said some health plans pay for the test. Quanterix declined to disclose a price, but said its test is much cheaper than specialized scans. All companies are trying to ensure wider insurance coverage. C2N and Quanterix say their tests are for cognitively impaired patients. Quest says its test is for people with or without symptoms. Many experts do not recommend the use of blood tests in asymptomatic people outside of trials, saying that not enough research has been done in this group. Quest spokeswoman Kimberly Gorode said the company relies on doctors “to use their discretion when ordering tests.” He added that the company believes the “clinical utility of the test will increase” if the FDA approves new treatments. Many neurologists take a wait-and-see approach even for patients with cognitive impairment. Jonathan D. Drake, associate director of the Alzheimer’s Disease and Memory Disorders Center at Lifespan’s Rhode Island Hospital in Providence, used C2N tests on more than three dozen patients in a company-sponsored study. He described his experience as positive, but said it’s too early to use the tests to make treatment or other decisions. “This is a brand new technology, and it will take some time to figure out how useful it really is, in what types of patients and under what kinds of conditions,” Drake said. Other doctors plan to use the tests once they are covered by Medicare and other insurances. Seth Keller, a neurologist in Lumberton, New Jersey, said he has diagnosed Alzheimer’s the same way for 30 years — with physical exams, interviews, questionnaires, brain scans and memory studies — but is troubled by the uncertainty. “I would beg for any test” that provides more specific information, said Keller, co-chair of the National Task Force on Intellectual Disabilities and Dementia Practices, a nonprofit advocacy organization. C2N, the small St. Louis biotech company that made the test used for Lynn, was founded in 2007 by two Washington University neurologists, Randall J. Bateman and David M. Holtzman, and Joel Braunstein, a cardiologist with experience in the field of life sciences. . Doctors can order the test, called PrecivityAD, for patients 60 and older who have memory or other cognitive problems. The test, company officials say, is designed to complement doctors’ assessments, not replace them. It arrives at clinics with a shoebox-sized kit equipped with a vial of blood, a cold pack and instructions. After the blood is collected, it is spun in a centrifuge to separate the plasma, the yellowish liquid part that is sent back to C2N. Doctors receive results within 10 days. On a recent day in the C2N lab, scientist Samantha Koch prepared plasma samples for analysis with mass spectrometers, instruments that identify compounds by molecular weight. For the Alzheimer’s test, the devices detect two types of amyloid and also determine whether a person has genetic variations that affect the risk of developing the disease. After adding the patient’s age, an algorithm produces an “amyloid probability score” that indicates the likelihood that the patient has plaques that would show up on an amyloid PET scan, the gold standard for diagnosing Alzheimer’s. About 10 to 15 percent of patients fall into a gray area that requires more evaluation, Braunstein said. Otherwise, the results agree with PET scans about 85 percent of the time, according to the company and studies published in April in the journal JAMA Network Open. C2N is close to launching a new, improved version of the test, based on Washington University research, that will also detect a form of tau, a protein whose toxic tangles are linked to Alzheimer’s disease. Amyloid-tau…
