Recently a patient inquired about p-Tau217 testing, so I’ve been doing a bit of a dive on the topic, and thought I’d share my thoughts on it.
First, a bit of background. p-Tau217 is a protein that is found in abundance in the brain of Alzheimer’s disease patients. One of the tests that a neurologist might do when evaluating if a patient has Alzheimer’s disease or not is a lumbar puncture (aka a “spinal tap”) in which they stick a needle into a patient’s spine, withdraw some fluid, and send it to the lab to test for p-Tau217 as well as other proteins that are elevated in Alzheimer’s disease.
Just within the past few weeks, p-Tau217 testing got a further boost with the publication of a paper in the prestigious journal JAMA. Researchers drew baseline p-Tau217 labs on several thousand healthy older people with no signs of dementia and then followed them up over a decade. They found that those with the highest baseline levels of p-Tau217 were the people most likely to develop dementia five and ten years later.
So far all of this sounds good. We have a simple blood test that can be used both to diagnose Alzheimer’s disease in those who have symptoms, and to predict who is at risk for it in those who do not. So everyone should have p-Tau217 testing as part of their annual physical, right?
Absolutely not. Let’s unpack why this test is hardly the miracle that it sounds like at first glance.
First off, the test costs between $300 and $400, and is usually not covered by insurance. So it’s simply not feasible at this time to regularly check for many people. But let’s leave that aside and get into the medical limitations.
The test is not as accurate as it seems at first glance. Like any test, there are a variety of issues, such as an acute infection (for example with a common cold) or an underactive kidney (very common in elderly adults) that can cause a false elevation of p-Tau levels.
Even leaving those circumstances aside, false positives are fairly common. The test only has a specificity of about 85%, meaning that in roughly 15% of normal cases, an elevated p-Tau217 will be detected in the blood. If suddenly millions of healthy people start getting p-Tau217 tests, we are going to see a tsunami of false positives. And keep in mind that those results will not be harmless, since they will lead many people to believe inaccurately that they are on the cusp of developing a fatal and incurable illness.
And then things get even more tricky, because although p-Tau217 is elevated in Alzheimer’s patients, some people who have elevated levels of p-Tau217 never develop Alzheimer’s. For example, in this recent study, even among patients with the highest p-Tau217 levels, 22% were dementia free a decade later (presumably some of these patients may still go on to develop dementia, but we don’t have long enough follow up on them to know for sure).
Taken in sum, this test can be falsely elevated for non-Alzheimer’s reasons like a cold or other stressor; can be falsely positive with some frequency even under optimal circumstances; and even when accurately positive, does not definitively predict who is at risk for Alzheimer’s and who is not.
By way of analogy, p-Tau217 seems to be much more like a cholesterol test than an HIV test. An HIV test is pretty definitive: either you have HIV or you don’t. A cholesterol test by contrast gives you some sense of your long-term risk for a cardiovascular event, but it is by no means definitive. Plenty of people have sky high cholesterol and live to an advanced age without any heart disease; others drop dead of a heart attack at a young age despite perfectly normal cholesterol. So while it’s worthwhile to know your cholesterol levels and consider them in the overall picture of your health, a cholesterol reading is not a precise predictor of your future. Ditto p-Tau217, which can at best give you some sense of your long-term risk for dementia, but cannot tell you with certainty if you will develop Alzheimer’s disease, nor when.
There’s another key point that I’d like to make about the cholesterol analogy: we have very effective treatments for lowering cholesterol, and studies showing that (in properly selected patients), doing so can cut the risk for actual heart attacks and strokes. We also know of many other measures that a person who is at high risk for heart attack or stroke can take to reduce their risk (diet, exercise, smoking cessation, medications to reduce blood pressure, a daily aspirin, etc). In other words, checking your cholesterol level does not just warn you that you might be at risk for a heart attack someday; it can actually guide you to take steps that may prevent that heart attack. We really have no such interventions for p-Tau and Alzheimer’s.
Research is ongoing and we may get there within the next few years, but at this point in time, there is simply nothing we can do about an abnormal p-Tau217 test. Getting diagnosed with a problem for which there is no treatment simply isn’t helpful for living a longer or happier life.
It’s worth noting that this newest JAMA study was in large part funded by pharmaceutical companies who are trying to develop drugs to lower p-Tau levels. This doesn’t mean the research is inherently flawed, nor that the test won’t someday turn out to be very useful. But it looks like these companies laying the groundwork for a time when doctors may treat p-Tau levels the same way we currently treat high cholesterol or high blood pressure. Certainly if their drugs pan out to reduce the risk for actual dementia cases, that could become a helpful approach – and one that earns the pharmaceutical companies astronomical profits. But until then, this test is best used sparingly, in patients who already have memory difficulties, with the goal of helping to distinguish Alzheimer’s from other causes of dementia. Even then it provides patients and their families an explanation and some prognostic information, but not (sadly, at this time) the potential for a cure.
