Alzheimer’s blood tests show ‘very good accuracy’ in early trials

One of the tests currently in development at Roche is the Elecsys Amyloid Plasma Panel, which measures Alzheimer’s disease biomarkers phosphorylated Tau (pTau) 181 protein and apolipoprotein E4 (ApoE4) in the blood.

“The Elecsys Amyloid Plasma Panel is a minimally invasive blood test that only requires a small amount of blood to run,” Carboni explained.

“The test checks levels of a protein known as pTau 181, which is found to accumulate at increased levels in the blood starting from the early symptoms of cognitive impairment. The same protein also accumulates in a person’s cerebrospinal fluid (CSF), which is what we currently test for with the Elecsys CSF test,” she detailed.

“The test also informs us of the presence of the gene ApoE4, which is one of the most common genetic risk factors for Alzheimer’s disease,” Carboni continued. “More recently, it has also been known to correlate with side effects of disease-modifying therapies for Alzheimer’s. A negative result with the test means patients are unlikely to have these hallmarks of Alzheimer’s and they should be investigated for other causes of cognitive decline.”

During this study of 492 participants across the United States and Europe, researchers found the panel was able to rule out Alzheimer’s disease with a high negative predictive value (NPV) of 96.2%.

“The results show that the test can accurately rule out amyloid pathology — a hallmark of Alzheimer’s — as a possible cause of cognitive decline symptoms with high certainty, offering reassurance with a simple blood test and avoiding unnecessary further testing,” according to Carboni.

The second test in development is the Elecsys pTau 217 assay, measuring another Alzheimer’s disease biomarker known as the phosphorylated Tau (pTau) 217 protein.

“pTau 217 is a protein found in the blood which is often at increased levels in the early stages of cognitive impairment,” Carboni explained.

“The head-to-head study was conducted because pTau 217 is currently under development as a ‘double cutoff’ biomarker test, meaning that the test returns both positive and negative results that you can trust with high degree of certainty (based on the clinical performance), but there is also an intermediate zone, where patients don’t get a positive or negative answer — they are somewhere in the middle.”

– Margherita Carboni, PhD

“This study was done to see if we could minimize this ‘greyzone’ by testing it against other tests,” she added. “Currently, experts say that tests need to keep this grey zone to a maximum of 30%, and the results from this study show this assay kept it around 12%.”

After reviewing the results of these two studies, Manisha Santosh Parulekar, MD, chief of the Division of Geriatrics and co-director of the Center for Memory Loss and Brain Health at Hackensack Meridian Neuroscience Institute at Hackensack University Medical Center in New Jersey, told MNT they were interesting, but not surprising.

“Prior research showed that pTau 181 levels in the blood are elevated in individuals with Alzheimer’s disease,” Parulekar explained. “A 2020 study published in Nature Medicine found that plasma pTau 181 levels were able to distinguish Alzheimer’s disease from healthy controls with high accuracy.”

“Additionally, individuals with one copy of the ApoE4 gene have a three-fold increased risk of developing Alzheimer’s disease, while those with two copies have a 12-fold increased risk,” she continued. “These assays, which measure plasma levels of pTau 181 and ApoE4, may eventually offer a less invasive and more accessible method for diagnosing Alzheimer’s disease.”

Parulekar said that continued research into new ways of screening for Alzheimer’s disease is essential for improving patient outcomes, reducing healthcare costs, and managing the growing public health challenge of this devastating disease.

“By developing more effective and accessible screening methods, we can ensure that individuals with Alzheimer’s disease receive the care and support they need as early as possible,” she added.

MNT also spoke with Clifford Segil, DO, a neurologist at Providence Saint John’s Health Center in Santa Monica, CA, about these studies.

Segil, who was not involved in the studies, said his first reaction was that it defies common sense for a practicing neurologist to rely on a blood test to support an early diagnosis of Alzheimer’s dementia.

“Patients are screened by neurologists for memory loss with an evaluation and neuroimaging, which may lead to the diagnosis of dementia [by] a neurologist,” he explained.

“Unfortunately, in the year 2024 there are not enough neurologists to evaluate and screen patients for dementia and new screening tools are needed,“ he added, noting, however, that “blood tests are not what clinical neurologists are looking for, but rather a series of tests which can be administered by primary care physicians or allied healthcare professionals.“

These, he suggested, “would be better than screening blood tests for dementia, which clinical neurologists will very [likely] never adapt.”

“The individuals noted in these tests should receive anti-amyloid medications to prove if the diagnosis and then treatment of a possible Alzheimer’s dementia patient has any discernible change in their memory loss,” Segil also advised.

Finally, he expressed the opinion that: “As the number of patients being treated with anti-amyloid medications increases, and postmarketing surveillance notes no discernible or significant improvement in these patients’ cognitive complaints, the emphasis of early diagnosis with amyloid tests will decrease, as clinicians have not accepted these tests to have any clinical utility at this time.”