Last month, The US Food and Drug Administration approved a new blood test for assisting the diagnosis of Alzheimer’s disease. Produced by Roche, Elecsys pTau181 measures the concentration of a specific molecule—a phosphorylated form of the tau protein—in the blood. Tau is one of two proteins, the other being amyloid, that become malformed and accumulate in the brains of patients with certain types of dementia. It is believed that the buildup of these proteins interferes with the communication of brain cells, leading to these patients’ symptoms.
The test had already received authorization in July for marketing in Europe and is thus the first early screening system for Alzheimer’s for use in primary care settings approved in the planet’s two major pharmaceutical markets. It is an opener in what should soon become a crowded field, as there are several other tests in advanced stages of testing and approval.
How Do Such Tests Work?
Elecsys pTau181 looks in the blood plasma for a form of the tau protein that has a phosphate group attached, which is often found in elevated amounts in Alzheimer’s patients. This molecule is an indirect marker of the plaques of amyloid and neurofibrillary tangles of tau observed in the brains of patients with the disease.
Some other tests have also been approved, though not for early screening. These assess other biomarkers that relate to these two proteins. One test, called Lumipulse and made by the 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 bottom line is that these tests offer clues to the probable presence of amyloidosis in the brain, which then needs to be diagnosed with greater accuracy using more invasive tests, such as a PET (positron emission tomography) scan and cerebrospinal fluid analysis by lumbar puncture, considered the clinical gold standard for diagnosing amyloid pathology in living patients. Even these, however, come with some degree of uncertainty; true diagnostic certainty can only be had with a post-mortem dissection of the brain.
Why Approve These Tests Now?
In the past, confirmation of an Alzheimer’s diagnosis was not that important, as there were no drugs or therapies that could alter the course of the disease. But with the approval of new Alzheimer’s monoclonal antibody treatments, the landscape has changed in the past few years.
To use these medicines, you need a way to confirm which patients can benefit. And since the drugs ideally yield the best results when used early on in the disease’s progression, a relatively inexpensive and minimally invasive diagnostic test will be extremely useful. Subjecting all elderly people with suspected symptoms of cognitive decline to PET scans and cerebrospinal fluid sampling is impractical, so this is where blood testing for Alzheimer’s comes in.
Just How Useful Are These Tests?
Elecsys pTau181 is the first test to be approved for use as a community-screening tool. The idea is for it to be administered at the primary care level—so, for instance, by a primary care physician or general practitioner. The test has been shown to have a good “negative predictive value”—that is, it is effective at accurately indicating who does not have amyloid disease. In settings where the overall prevalence of amyloid disease is low, a negative result from this test is 97.9 percent reliable. This makes it useful for selecting which patients to put forward for further testing.
The results are similar to those of other tests that have already been approved in recent months, such as Lumipulse from Japan’s Fujirebio, which in trials has shown a negative predictive value of about 97 percent.
However, there is an important limitation to note: for all blood tests for Alzheimer’s, there tends to be a relatively large proportion of patients (15-30 percent is a common estimate) who fall into a gray area of uncertainty, in which the levels of identified biomarkers do not allow for either a positive or a negative answer.