More last month US Food and Drug Administration Approved New blood test to help diagnose Alzheimer’s disease. Elecsys pTau181, produced by Roche, measures the concentration of a specific molecule (the phosphorylated form of the tau protein) in the blood. Tau is one of two proteins that malform and build up in the brains of people with certain types of dementia, the other being amyloid. It is believed that the buildup of these proteins interferes with the communication of brain cells, causing these patients’ symptoms.
The test was already approved for sale in Europe in July, making it the first Alzheimer’s early screening system for use in primary care settings to be approved in the two major pharmaceutical markets on the planet. This is the beginning of what will soon become a crowded field, as there are several different tests at advanced stages of testing and approval.
How do these tests work?
Elecsys pTau181 detects forms of tau protein with attached phosphate groups in plasma. This tau protein is often found in high amounts in Alzheimer’s patients. This molecule is an indirect marker of amyloid plaques and tau neurofibrillary tangles observed in the brains of patients with the disease.
Some other tests are also approved, but not for early screening. They evaluate other biomarkers associated with these two proteins. The test, called Lumipulse, made by Japanese company Fujirebio, looks at the ratio between another form of phosphorylated tau (pTau217) and a key protein fragment that forms amyloid plaques (amyloid beta peptide 1-42).
The point is that these tests provide clues about the possible presence of amyloidosis in the brain, which should be diagnosed more accurately using more invasive tests, such as PET (positron emission tomography) scans and cerebrospinal fluid analysis through lumbar puncture. It is considered the clinical gold standard for diagnosing amyloid pathology in living patients. But even these pose some degree of uncertainty. True diagnostic certainty can only be achieved through postmortem brain dissection.
Why should we approve this test now?
In the past, confirming a diagnosis of Alzheimer’s disease was not as important. Because there were no drugs or treatments that could change the course of the disease. But that has changed in the past few years with the approval of new Alzheimer’s monoclonal antibody treatments.
Using these medicines requires a way to determine which patients may benefit. And since using drugs early in the disease process would ideally yield the best results, relatively inexpensive, minimally invasive diagnostic tests would be very useful. Because it is impractical to perform PET scans and cerebrospinal fluid sampling on all older adults with suspected symptoms of cognitive decline, blood testing for Alzheimer’s disease is warranted.
How useful is this test?
Elecsys pTau181 is the first test approved for use as a community screening tool. The idea is for it to be managed at the primary care level, i.e. by a primary care physician or general practitioner. This test has been shown to have a good “negative predictive value.” In other words, it’s effective at indicating exactly who is who. not so I have amyloid disease. In settings where the overall prevalence of amyloid disease is low, a negative result from this test is 97.9% reliable. This is useful in selecting which patients to submit for further testing.
The results are similar to those of other tests already approved in recent months, such as Japan’s Fujirebio’s Lumipulse, which showed a negative predictive value of about 97% in the test.
However, there are important limitations to note. For all blood tests for Alzheimer’s disease, there tends to be a relatively large proportion of patients whose levels of identified biomarkers fall into a gray area of uncertainty that does not allow for a positive or negative answer (15-30% is a typical estimate).
